[{"file_date_updated":"2022-08-05T05:56:03Z","license":"https://creativecommons.org/licenses/by/4.0/","article_number":"102350","author":[{"last_name":"Kampjut","first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen"},{"full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-08-03T06:31:06Z","date_created":"2022-04-15T09:32:35Z","volume":74,"year":"2022","pmid":1,"publication_status":"published","publisher":"Elsevier","department":[{"_id":"LeSa"}],"month":"06","publication_identifier":{"issn":["0959-440X"]},"doi":"10.1016/j.sbi.2022.102350","language":[{"iso":"eng"}],"external_id":{"isi":["000829029500020"],"pmid":["35316665"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","abstract":[{"lang":"eng","text":"Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I."}],"type":"journal_article","oa_version":"Published Version","file":[{"success":1,"checksum":"72bdde48853643a32d42b75f54965c44","date_updated":"2022-08-05T05:56:03Z","date_created":"2022-08-05T05:56:03Z","file_id":"11725","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":815607,"access_level":"open_access","file_name":"2022_CurrentOpStructBiology_Kampjut.pdf"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"11167","title":"Structure of respiratory complex I – An emerging blueprint for the mechanism","ddc":["570"],"status":"public","intvolume":" 74","day":"01","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","scopus_import":"1","keyword":["Molecular Biology","Structural Biology"],"date_published":"2022-06-01T00:00:00Z","publication":"Current Opinion in Structural Biology","citation":{"short":"D. Kampjut, L.A. Sazanov, Current Opinion in Structural Biology 74 (2022).","mla":"Kampjut, Domen, and Leonid A. Sazanov. “Structure of Respiratory Complex I – An Emerging Blueprint for the Mechanism.” Current Opinion in Structural Biology, vol. 74, 102350, Elsevier, 2022, doi:10.1016/j.sbi.2022.102350.","chicago":"Kampjut, Domen, and Leonid A Sazanov. “Structure of Respiratory Complex I – An Emerging Blueprint for the Mechanism.” Current Opinion in Structural Biology. Elsevier, 2022. https://doi.org/10.1016/j.sbi.2022.102350.","ama":"Kampjut D, Sazanov LA. Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. 2022;74. doi:10.1016/j.sbi.2022.102350","apa":"Kampjut, D., & Sazanov, L. A. (2022). Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. Elsevier. https://doi.org/10.1016/j.sbi.2022.102350","ieee":"D. Kampjut and L. A. Sazanov, “Structure of respiratory complex I – An emerging blueprint for the mechanism,” Current Opinion in Structural Biology, vol. 74. Elsevier, 2022.","ista":"Kampjut D, Sazanov LA. 2022. Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. 74, 102350."},"article_type":"original"},{"type":"journal_article","issue":"1","abstract":[{"text":"Imbalanced mitochondrial dNTP pools are known players in the pathogenesis of multiple human diseases. Here we show that, even under physiological conditions, dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues and human cultured cells. In addition, a vast majority of mitochondrial dGTP is tightly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. NDUFA10 shares a deoxyribonucleoside kinase (dNK) domain with deoxyribonucleoside kinases in the nucleotide salvage pathway, though no specific function beyond stabilizing the complex I holoenzyme has been described for this subunit. We mutated the dNK domain of NDUFA10 in human HEK-293T cells while preserving complex I assembly and activity. The NDUFA10E160A/R161A shows reduced dGTP binding capacity in vitro and leads to a 50% reduction in mitochondrial dGTP content, proving that most dGTP is directly bound to the dNK domain of NDUFA10. This interaction may represent a hitherto unknown mechanism regulating mitochondrial dNTP availability and linking oxidative metabolism to DNA maintenance.","lang":"eng"}],"intvolume":" 5","status":"public","title":"Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit","ddc":["570"],"_id":"11551","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"access_level":"open_access","file_name":"2022_communicationsbiology_Molina-Granada.pdf","content_type":"application/pdf","file_size":2335369,"creator":"kschuh","relation":"main_file","file_id":"11571","checksum":"965f88bbcef3fd0c3e121340555c4467","success":1,"date_updated":"2022-07-13T07:44:58Z","date_created":"2022-07-13T07:44:58Z"}],"oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"23","citation":{"ama":"Molina-Granada D, González-Vioque E, Dibley MG, et al. Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications Biology. 2022;5(1). doi:10.1038/s42003-022-03568-6","ista":"Molina-Granada D, González-Vioque E, Dibley MG, Cabrera-Pérez R, Vallbona-Garcia A, Torres-Torronteras J, Sazanov LA, Ryan MT, Cámara Y, Martí R. 2022. Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications Biology. 5(1), 620.","apa":"Molina-Granada, D., González-Vioque, E., Dibley, M. G., Cabrera-Pérez, R., Vallbona-Garcia, A., Torres-Torronteras, J., … Martí, R. (2022). Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-022-03568-6","ieee":"D. Molina-Granada et al., “Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit,” Communications Biology, vol. 5, no. 1. Springer Nature, 2022.","mla":"Molina-Granada, David, et al. “Most Mitochondrial DGTP Is Tightly Bound to Respiratory Complex I through the NDUFA10 Subunit.” Communications Biology, vol. 5, no. 1, 620, Springer Nature, 2022, doi:10.1038/s42003-022-03568-6.","short":"D. Molina-Granada, E. González-Vioque, M.G. Dibley, R. Cabrera-Pérez, A. Vallbona-Garcia, J. Torres-Torronteras, L.A. Sazanov, M.T. Ryan, Y. Cámara, R. Martí, Communications Biology 5 (2022).","chicago":"Molina-Granada, David, Emiliano González-Vioque, Marris G. Dibley, Raquel Cabrera-Pérez, Antoni Vallbona-Garcia, Javier Torres-Torronteras, Leonid A Sazanov, Michael T. Ryan, Yolanda Cámara, and Ramon Martí. “Most Mitochondrial DGTP Is Tightly Bound to Respiratory Complex I through the NDUFA10 Subunit.” Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03568-6."},"publication":"Communications Biology","date_published":"2022-06-23T00:00:00Z","article_number":"620","file_date_updated":"2022-07-13T07:44:58Z","department":[{"_id":"LeSa"}],"publisher":"Springer Nature","publication_status":"published","pmid":1,"year":"2022","acknowledgement":"We thank Dr, Luke Formosa (Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia) for his valuable advice and assistance on NDUFA10 molecular studies and Dr. Francesc Canals and his team (Proteomics Laboratory, Vall d’Hebron Institute of Oncology [VHIO], Universitat Autònoma de Barcelona, Barcelona, Spain) for their assistance with LC-MS/MS analyses. This work was supported by the Spanish Ministry of Industry, Economy and Competitiveness [grants BFU2014-52618-R, SAF2017-87506, and PID2020-112929RB-I00 to Y.C.], by the Spanish Instituto de Salud Carlos III [grants PI21/00554 and PMP15/00025 to R.M.], co-financed by the European Regional Development Fund (ERDF), and by an NHMRC Project grant to M.R. (GNT1164459).\r\n","volume":5,"date_updated":"2023-08-03T11:51:58Z","date_created":"2022-07-10T22:01:52Z","author":[{"full_name":"Molina-Granada, David","first_name":"David","last_name":"Molina-Granada"},{"full_name":"González-Vioque, Emiliano","last_name":"González-Vioque","first_name":"Emiliano"},{"full_name":"Dibley, Marris G.","first_name":"Marris G.","last_name":"Dibley"},{"full_name":"Cabrera-Pérez, Raquel","first_name":"Raquel","last_name":"Cabrera-Pérez"},{"full_name":"Vallbona-Garcia, Antoni","last_name":"Vallbona-Garcia","first_name":"Antoni"},{"full_name":"Torres-Torronteras, Javier","first_name":"Javier","last_name":"Torres-Torronteras"},{"full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A","last_name":"Sazanov"},{"full_name":"Ryan, Michael T.","last_name":"Ryan","first_name":"Michael T."},{"first_name":"Yolanda","last_name":"Cámara","full_name":"Cámara, Yolanda"},{"full_name":"Martí, Ramon","last_name":"Martí","first_name":"Ramon"}],"publication_identifier":{"eissn":["23993642"]},"month":"06","isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":[" 35739187"],"isi":["000815098500002"]},"language":[{"iso":"eng"}],"doi":"10.1038/s42003-022-03568-6"},{"publication_identifier":{"issn":["2050-5698"],"eissn":["2050-5701"]},"month":"10","doi":"10.1093/jmicro/dfac037","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["35861182"],"isi":["000837950900001"]},"isi":1,"quality_controlled":"1","file_date_updated":"2023-02-03T08:34:48Z","author":[{"first_name":"Christoph","last_name":"Gerle","full_name":"Gerle, Christoph"},{"first_name":"Jun-ichi","last_name":"Kishikawa","full_name":"Kishikawa, Jun-ichi"},{"full_name":"Yamaguchi, Tomoko","first_name":"Tomoko","last_name":"Yamaguchi"},{"first_name":"Atsuko","last_name":"Nakanishi","full_name":"Nakanishi, Atsuko"},{"full_name":"Çoruh, Mehmet Orkun","orcid":"0000-0002-3219-2022","id":"d25163e5-8d53-11eb-a251-e6dd8ea1b8ef","last_name":"Çoruh","first_name":"Mehmet Orkun"},{"first_name":"Fumiaki","last_name":"Makino","full_name":"Makino, Fumiaki"},{"full_name":"Miyata, Tomoko","last_name":"Miyata","first_name":"Tomoko"},{"last_name":"Kawamoto","first_name":"Akihiro","full_name":"Kawamoto, Akihiro"},{"first_name":"Ken","last_name":"Yokoyama","full_name":"Yokoyama, Ken"},{"last_name":"Namba","first_name":"Keiichi","full_name":"Namba, Keiichi"},{"first_name":"Genji","last_name":"Kurisu","full_name":"Kurisu, Genji"},{"first_name":"Takayuki","last_name":"Kato","full_name":"Kato, Takayuki"}],"volume":71,"date_updated":"2023-08-03T12:13:37Z","date_created":"2022-07-25T10:04:58Z","pmid":1,"year":"2022","acknowledgement":"Cyclic Innovation for Clinical Empowerment (JP17pc0101020 from Japan Agency for Medical Research and Development (AMED) to K.N. and G.K.); Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research) from AMED (JP20am0101117 to K.N., JP16K07266 to Atsunori Oshima and C.G., JP22ama121001j0001 to Masaki Yamamoto, G.K., T.K. and C.G.); a JSPS KAHKENHI\r\ngrant (20K06514 to J.K.) and a Grant-in-aid for JSPS fellows (20J00162 to A.N.).\r\nWe are grateful for initiation and scientific support from Matthias Rogner, Marc M. Nowaczyk, Anna Frank and ̈Yuko Misumi for the PSI monomer project and also would like to thank Hideki Shigematsu for critical reading of the manuscript. And we are indebted to the two anonymous reviewers who helped us to improve our manuscript.","department":[{"_id":"LeSa"}],"publisher":"Oxford University Press","publication_status":"published","has_accepted_license":"1","article_processing_charge":"No","day":"01","scopus_import":"1","keyword":["Radiology","Nuclear Medicine and imaging","Instrumentation","Structural Biology"],"date_published":"2022-10-01T00:00:00Z","citation":{"mla":"Gerle, Christoph, et al. “Structures of Multisubunit Membrane Complexes with the CRYO ARM 200.” Microscopy, vol. 71, no. 5, Oxford University Press, 2022, pp. 249–61, doi:10.1093/jmicro/dfac037.","short":"C. Gerle, J. Kishikawa, T. Yamaguchi, A. Nakanishi, M.O. Çoruh, F. Makino, T. Miyata, A. Kawamoto, K. Yokoyama, K. Namba, G. Kurisu, T. Kato, Microscopy 71 (2022) 249–261.","chicago":"Gerle, Christoph, Jun-ichi Kishikawa, Tomoko Yamaguchi, Atsuko Nakanishi, Mehmet Orkun Çoruh, Fumiaki Makino, Tomoko Miyata, et al. “Structures of Multisubunit Membrane Complexes with the CRYO ARM 200.” Microscopy. Oxford University Press, 2022. https://doi.org/10.1093/jmicro/dfac037.","ama":"Gerle C, Kishikawa J, Yamaguchi T, et al. Structures of multisubunit membrane complexes with the CRYO ARM 200. Microscopy. 2022;71(5):249-261. doi:10.1093/jmicro/dfac037","ista":"Gerle C, Kishikawa J, Yamaguchi T, Nakanishi A, Çoruh MO, Makino F, Miyata T, Kawamoto A, Yokoyama K, Namba K, Kurisu G, Kato T. 2022. Structures of multisubunit membrane complexes with the CRYO ARM 200. Microscopy. 71(5), 249–261.","ieee":"C. Gerle et al., “Structures of multisubunit membrane complexes with the CRYO ARM 200,” Microscopy, vol. 71, no. 5. Oxford University Press, pp. 249–261, 2022.","apa":"Gerle, C., Kishikawa, J., Yamaguchi, T., Nakanishi, A., Çoruh, M. O., Makino, F., … Kato, T. (2022). Structures of multisubunit membrane complexes with the CRYO ARM 200. Microscopy. Oxford University Press. https://doi.org/10.1093/jmicro/dfac037"},"publication":"Microscopy","page":"249-261","article_type":"original","issue":"5","abstract":[{"lang":"eng","text":"Progress in structural membrane biology has been significantly accelerated by the ongoing 'Resolution Revolution' in cryo electron microscopy (cryo-EM). In particular, structure determination by single particle analysis has evolved into the most powerful method for atomic model building of multisubunit membrane protein complexes. This has created an ever increasing demand in cryo-EM machine time, which to satisfy is in need of new and affordable cryo electron microscopes. Here, we review our experience in using the JEOL CRYO ARM 200 prototype for the structure determination by single particle analysis of three different multisubunit membrane complexes: the Thermus thermophilus V-type ATPase VO complex, the Thermosynechococcus elongatus photosystem I monomer and the flagellar motor LP-ring from Salmonella enterica."}],"type":"journal_article","oa_version":"Published Version","file":[{"success":1,"checksum":"23b51c163636bf9313f7f0818312e67e","date_created":"2023-02-03T08:34:48Z","date_updated":"2023-02-03T08:34:48Z","file_id":"12498","relation":"main_file","creator":"dernst","file_size":7812696,"content_type":"application/pdf","access_level":"open_access","file_name":"2022_Microscopy_Gerle.pdf"}],"_id":"11648","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 71","ddc":["570"],"title":"Structures of multisubunit membrane complexes with the CRYO ARM 200","status":"public"},{"abstract":[{"text":"Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria1. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane2, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a ‘domino effect’ series of proton transfers and electrostatic interactions: the forward wave (‘dominoes stacking’) primes the pump, and the reverse wave (‘dominoes falling’) results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes.","lang":"eng"}],"issue":"7928","type":"journal_article","oa_version":"Submitted Version","file":[{"access_level":"open_access","file_name":"EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf","file_size":1425655,"content_type":"application/pdf","creator":"lsazanov","relation":"main_file","file_id":"13104","checksum":"d42a93e24f59e883ef0b5429832391d0","success":1,"date_created":"2023-05-30T17:05:31Z","date_updated":"2023-05-30T17:05:31Z"},{"file_id":"13105","relation":"main_file","success":1,"checksum":"5422bc0a73b3daadafa262c7ea6deae3","date_updated":"2023-05-30T17:07:05Z","date_created":"2023-05-30T17:07:05Z","access_level":"open_access","file_name":"EcCxI_manuscript_rev3_SI_All_opt_upd.pdf","creator":"lsazanov","content_type":"application/pdf","file_size":9842513}],"_id":"12138","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","title":"A universal coupling mechanism of respiratory complex I","ddc":["572"],"intvolume":" 609","day":"22","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","keyword":["Multidisciplinary"],"date_published":"2022-09-22T00:00:00Z","publication":"Nature","citation":{"ama":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. A universal coupling mechanism of respiratory complex I. Nature. 2022;609(7928):808-814. doi:10.1038/s41586-022-05199-7","ieee":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, and L. A. Sazanov, “A universal coupling mechanism of respiratory complex I,” Nature, vol. 609, no. 7928. Springer Nature, pp. 808–814, 2022.","apa":"Kravchuk, V., Petrova, O., Kampjut, D., Wojciechowska-Bason, A., Breese, Z., & Sazanov, L. A. (2022). A universal coupling mechanism of respiratory complex I. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-05199-7","ista":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. 2022. A universal coupling mechanism of respiratory complex I. Nature. 609(7928), 808–814.","short":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, L.A. Sazanov, Nature 609 (2022) 808–814.","mla":"Kravchuk, Vladyslav, et al. “A Universal Coupling Mechanism of Respiratory Complex I.” Nature, vol. 609, no. 7928, Springer Nature, 2022, pp. 808–14, doi:10.1038/s41586-022-05199-7.","chicago":"Kravchuk, Vladyslav, Olga Petrova, Domen Kampjut, Anna Wojciechowska-Bason, Zara Breese, and Leonid A Sazanov. “A Universal Coupling Mechanism of Respiratory Complex I.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-05199-7."},"article_type":"original","page":"808-814","file_date_updated":"2023-05-30T17:07:05Z","ec_funded":1,"author":[{"full_name":"Kravchuk, Vladyslav","last_name":"Kravchuk","first_name":"Vladyslav","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Olga","last_name":"Petrova","id":"5D8C9660-5D49-11EA-8188-567B3DDC885E","full_name":"Petrova, Olga"},{"last_name":"Kampjut","first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen"},{"last_name":"Wojciechowska-Bason","first_name":"Anna","full_name":"Wojciechowska-Bason, Anna"},{"last_name":"Breese","first_name":"Zara","full_name":"Breese, Zara"},{"last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A"}],"related_material":{"link":[{"url":"https://doi.org/10.1038/s41586-022-05457-8","relation":"erratum"},{"url":"https://ista.ac.at/en/news/proton-dominos-kick-off-life/","description":"News on ISTA website","relation":"press_release"}],"record":[{"relation":"dissertation_contains","status":"public","id":"12781"}]},"date_updated":"2023-08-04T08:54:52Z","date_created":"2023-01-12T12:04:33Z","volume":609,"year":"2022","acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank V.-V. Hodirnau from IST Austria EMF, M. Babiak from CEITEC for assistance with collecting cryo-EM data and A. Charnagalov for the assistance with protein purification. V.K. was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria. V.K. and O.P. are funded by the ERC Advanced Grant 101020697 RESPICHAIN to L.S. This work was also supported by the Medical Research Council (UK).","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"LeSa"}],"month":"09","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"doi":"10.1038/s41586-022-05199-7","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"language":[{"iso":"eng"}],"external_id":{"isi":["000854788200001"],"pmid":["36104567"]},"oa":1,"quality_controlled":"1","isi":1,"project":[{"name":"Structural characterization of E. coli complex I: an important mechanistic model","grant_number":"25541","_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","name":"Structure and mechanism of respiratory chain molecular machines","grant_number":"101020697","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3"}]},{"scopus_import":"1","keyword":["Immunology","Immunology and Allergy","COVID-19","SARS-CoV-2","synthetic library","RBD","neutralization nanobody","VHH"],"day":"16","article_processing_charge":"No","has_accepted_license":"1","publication":"Frontiers in Immunology","citation":{"short":"D. Dormeshkin, M. Shapira, S. Dubovik, A. Kavaleuski, M. Katsin, A. Migas, A. Meleshko, S. Semyonov, Frontiers in Immunology 13 (2022).","mla":"Dormeshkin, Dmitri, et al. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology, vol. 13, 965446, Frontiers Media, 2022, doi:10.3389/fimmu.2022.965446.","chicago":"Dormeshkin, Dmitri, Michail Shapira, Simon Dubovik, Anton Kavaleuski, Mikalai Katsin, Alexandr Migas, Alexander Meleshko, and Sergei Semyonov. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology. Frontiers Media, 2022. https://doi.org/10.3389/fimmu.2022.965446.","ama":"Dormeshkin D, Shapira M, Dubovik S, et al. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 2022;13. doi:10.3389/fimmu.2022.965446","ieee":"D. Dormeshkin et al., “Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library,” Frontiers in Immunology, vol. 13. Frontiers Media, 2022.","apa":"Dormeshkin, D., Shapira, M., Dubovik, S., Kavaleuski, A., Katsin, M., Migas, A., … Semyonov, S. (2022). Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. Frontiers Media. https://doi.org/10.3389/fimmu.2022.965446","ista":"Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. 2022. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 13, 965446."},"article_type":"original","date_published":"2022-09-16T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\\ml and 9.6 ng\\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants."}],"_id":"12252","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library","status":"public","ddc":["570"],"intvolume":" 13","oa_version":"Published Version","file":[{"file_id":"12443","relation":"main_file","date_created":"2023-01-30T09:22:26Z","date_updated":"2023-01-30T09:22:26Z","success":1,"checksum":"f8f5d8110710033d0532e7e08bf9dad4","file_name":"2022_FrontiersImmunology_Dormeshkin.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":5695892}],"month":"09","publication_identifier":{"issn":["1664-3224"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000862479100001"]},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.3389/fimmu.2022.965446","language":[{"iso":"eng"}],"article_number":"965446","file_date_updated":"2023-01-30T09:22:26Z","acknowledgement":"The authors declare that this study received funding from Immunofusion. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.","year":"2022","publication_status":"published","department":[{"_id":"LeSa"}],"publisher":"Frontiers Media","author":[{"full_name":"Dormeshkin, Dmitri","last_name":"Dormeshkin","first_name":"Dmitri"},{"full_name":"Shapira, Michail","last_name":"Shapira","first_name":"Michail"},{"first_name":"Simon","last_name":"Dubovik","full_name":"Dubovik, Simon"},{"orcid":"0000-0003-2091-526X","id":"4968f7ad-eb97-11eb-a6c2-8ed382e8912c","last_name":"Kavaleuski","first_name":"Anton","full_name":"Kavaleuski, Anton"},{"first_name":"Mikalai","last_name":"Katsin","full_name":"Katsin, Mikalai"},{"first_name":"Alexandr","last_name":"Migas","full_name":"Migas, Alexandr"},{"first_name":"Alexander","last_name":"Meleshko","full_name":"Meleshko, Alexander"},{"full_name":"Semyonov, Sergei","first_name":"Sergei","last_name":"Semyonov"}],"date_created":"2023-01-16T09:56:57Z","date_updated":"2023-08-04T09:49:24Z","volume":13},{"type":"journal_article","issue":"8","abstract":[{"lang":"eng","text":"From a simple thought to a multicellular movement"}],"intvolume":" 135","status":"public","title":"Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole","_id":"12282","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None","scopus_import":"1","article_processing_charge":"No","day":"19","article_type":"letter_note","citation":{"short":"N. Amberg, M.A. Stouffer, I. Vercellino, Journal of Cell Science 135 (2022).","mla":"Amberg, Nicole, et al. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science, vol. 135, no. 8, 260017, The Company of Biologists, 2022, doi:10.1242/jcs.260017.","chicago":"Amberg, Nicole, Melissa A Stouffer, and Irene Vercellino. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.260017.","ama":"Amberg N, Stouffer MA, Vercellino I. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 2022;135(8). doi:10.1242/jcs.260017","ieee":"N. Amberg, M. A. Stouffer, and I. Vercellino, “Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole,” Journal of Cell Science, vol. 135, no. 8. The Company of Biologists, 2022.","apa":"Amberg, N., Stouffer, M. A., & Vercellino, I. (2022). Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260017","ista":"Amberg N, Stouffer MA, Vercellino I. 2022. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 135(8), 260017."},"publication":"Journal of Cell Science","date_published":"2022-04-19T00:00:00Z","article_number":"260017","publisher":"The Company of Biologists","department":[{"_id":"SiHi"},{"_id":"LeSa"}],"publication_status":"published","pmid":1,"acknowledgement":"The authors want to thank Professors Carrie Bernecky, Tom Henzinger, Martin Loose and Gaia Novarino for accepting to be interviewed, thus giving significant contribution to the discussion that lead to this article.","year":"2022","volume":135,"date_created":"2023-01-16T10:03:14Z","date_updated":"2023-08-04T10:28:04Z","author":[{"full_name":"Amberg, Nicole","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stouffer, Melissa A","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","last_name":"Stouffer","first_name":"Melissa A"},{"full_name":"Vercellino, Irene","first_name":"Irene","last_name":"Vercellino","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5618-3449"}],"publication_identifier":{"eissn":["1477-9137"],"issn":["0021-9533"]},"month":"04","quality_controlled":"1","isi":1,"external_id":{"isi":["000798123600015"],"pmid":["35438168"]},"language":[{"iso":"eng"}],"doi":"10.1242/jcs.260017"},{"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.3390/colorants1020010","month":"04","publication_identifier":{"issn":["2079-6447"]},"publication_status":"published","department":[{"_id":"LeSa"}],"publisher":"MDPI","year":"2022","acknowledgement":"This research was partly funded by Hacettepe University (Bilimsel Ara¸stırma Projeleri\r\nKoordinasyon Birimi), grant number FHD-2015-8094.The authors are indebted to Ahmet Önal for his supports in acquiring the fluorescence spectra and the decision of excitation wavelengths. The authors also acknowledge use of the services and facilities of UNAM-National Nanotechnology Research Center at Bilkent University and mica donation from Sabuncular Mining Co.","date_updated":"2023-08-09T10:12:22Z","date_created":"2022-04-04T09:03:54Z","volume":1,"author":[{"last_name":"Çoruh","first_name":"Mehmet Orkun","orcid":"0000-0002-3219-2022","id":"d25163e5-8d53-11eb-a251-e6dd8ea1b8ef","full_name":"Çoruh, Mehmet Orkun"},{"full_name":"Gündüz, Güngör","first_name":"Güngör","last_name":"Gündüz"},{"full_name":"Çolak, Üner","last_name":"Çolak","first_name":"Üner"},{"full_name":"Maviş, Bora","last_name":"Maviş","first_name":"Bora"}],"file_date_updated":"2022-04-04T10:39:24Z","article_type":"original","page":"149-164","publication":"Colorants","citation":{"mla":"Çoruh, Mehmet Orkun, et al. “PH-Dependent Coloring of Combination Effect Pigments with Anthocyanins from Brassica Oleracea Var. Capitata F. Rubra.” Colorants, vol. 1, no. 2, MDPI, 2022, pp. 149–64, doi:10.3390/colorants1020010.","short":"M.O. Çoruh, G. Gündüz, Ü. Çolak, B. Maviş, Colorants 1 (2022) 149–164.","chicago":"Çoruh, Mehmet Orkun, Güngör Gündüz, Üner Çolak, and Bora Maviş. “PH-Dependent Coloring of Combination Effect Pigments with Anthocyanins from Brassica Oleracea Var. Capitata F. Rubra.” Colorants. MDPI, 2022. https://doi.org/10.3390/colorants1020010.","ama":"Çoruh MO, Gündüz G, Çolak Ü, Maviş B. pH-dependent coloring of combination effect pigments with anthocyanins from Brassica oleracea var. capitata F. rubra. Colorants. 2022;1(2):149-164. doi:10.3390/colorants1020010","ista":"Çoruh MO, Gündüz G, Çolak Ü, Maviş B. 2022. pH-dependent coloring of combination effect pigments with anthocyanins from Brassica oleracea var. capitata F. rubra. Colorants. 1(2), 149–164.","apa":"Çoruh, M. O., Gündüz, G., Çolak, Ü., & Maviş, B. (2022). pH-dependent coloring of combination effect pigments with anthocyanins from Brassica oleracea var. capitata F. rubra. Colorants. MDPI. https://doi.org/10.3390/colorants1020010","ieee":"M. O. Çoruh, G. Gündüz, Ü. Çolak, and B. Maviş, “pH-dependent coloring of combination effect pigments with anthocyanins from Brassica oleracea var. capitata F. rubra,” Colorants, vol. 1, no. 2. MDPI, pp. 149–164, 2022."},"date_published":"2022-04-01T00:00:00Z","day":"01","article_processing_charge":"Yes","has_accepted_license":"1","status":"public","ddc":["570"],"title":"pH-dependent coloring of combination effect pigments with anthocyanins from Brassica oleracea var. capitata F. rubra","intvolume":" 1","_id":"10945","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"success":1,"checksum":"2c15c8d3041ebc36bc64870247081758","date_created":"2022-04-04T10:39:24Z","date_updated":"2022-04-04T10:39:24Z","file_id":"10949","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":2437988,"access_level":"open_access","file_name":"2022_Colorants_Coruh.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Mica-titania pearlescent pigments (MTs) were previously coated with organic molecules to obtain combination pigments (CPs) for achieving certain improvements or functionalities. Anthocyanins (ACNs) are molecules that can be extracted from natural resources and exhibit color changes via pH modifications of the enclosing medium. The purpose of the study was to produce a new series of CPs by depositing ACNs on MTs at different pH values, to observe the changes in color, and to associate these changes to thermogravimetrically determined deposition efficiencies in light of spectral differences. The extraction and deposition methods were based on aqueous chemistry and were straightforward. The ACN deposition generally increased with increasing pH and correlated with the consistency between the charges of the MT surfaces and the dominant ACN species at a specific pH value. The fluorescence of the CPs was inversely correlated with the deposition quantities invoking the possibility of a quenching effect.","lang":"eng"}],"issue":"2"},{"publisher":"Springer Nature","department":[{"_id":"GradSch"},{"_id":"LeSa"}],"publication_status":"published","pmid":1,"acknowledgement":"This study was financially supported by the State Committee on Science and Technology. We would like to thank Elena Tumar and Elena Kisileva at the Institute of Bioorganic Chemistry of NASB for their kind assistance with mouse immunizations.","year":"2022","volume":106,"date_created":"2022-06-26T22:01:34Z","date_updated":"2023-10-10T07:15:02Z","author":[{"first_name":"Dmitri","last_name":"Dormeshkin","full_name":"Dormeshkin, Dmitri"},{"last_name":"Shapira","first_name":"Michail","full_name":"Shapira, Michail"},{"last_name":"Karputs","first_name":"Alena","full_name":"Karputs, Alena"},{"full_name":"Kavaleuski, Anton","orcid":"0000-0003-2091-526X","id":"62304f89-eb97-11eb-a6c2-8903dd183976","last_name":"Kavaleuski","first_name":"Anton"},{"full_name":"Kuzminski, Ivan","last_name":"Kuzminski","first_name":"Ivan"},{"full_name":"Stepanova, Elena","first_name":"Elena","last_name":"Stepanova"},{"full_name":"Gilep, Andrei","last_name":"Gilep","first_name":"Andrei"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000813677500001"],"pmid":["35723693"]},"language":[{"iso":"eng"}],"doi":"10.1007/s00253-022-12022-w","publication_identifier":{"eissn":["1432-0614"],"issn":["0175-7598"]},"month":"08","intvolume":" 106","status":"public","title":"Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development","_id":"11462","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"None","type":"journal_article","abstract":[{"text":"Nanobodies (VHH) from camelid antibody libraries hold great promise as therapeutic agents and components of immunoassay systems. Synthetic antibody libraries that could be designed and generated once and for various applications could yield binders to virtually any targets, even for non-immunogenic or toxic ones, in a short term. One of the most difficult tasks is to obtain antibodies with a high affinity and specificity to polyglycosylated proteins. It requires antibody libraries with extremely high functional diversity and the use of sophisticated selection techniques. Here we report a development of a novel sandwich immunoassay involving a combination of the synthetic library-derived VHH-Fc fusion protein as a capture antibody and the immune single-chain fragment variable (scFv) as a tracer for the detection of pregnancy-associated glycoprotein (PAG) of cattle (Bos taurus). We succeeded in the generation of a number of specific scFv antibodies against PAG from the mouse immune library. Subsequent selection using the immobilized scFv-Fc capture antibody allowed to isolate 1.9 nM VHH binder from the diverse synthetic library without any overlapping with the capture antibody binding site. The prototype sandwich ELISA based on the synthetic VHH and the immune scFv was established. This is the first successful example of the combination of synthetic and immune antibody libraries in a single sandwich immunoassay. Thus, our approach could be used for the express isolation of antibody pairs and the development of sandwich immunoassays for challenging antigens.","lang":"eng"}],"page":"5093-5103","article_type":"original","citation":{"ama":"Dormeshkin D, Shapira M, Karputs A, et al. Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development. Applied Microbiology and Biotechnology. 2022;106:5093-5103. doi:10.1007/s00253-022-12022-w","ista":"Dormeshkin D, Shapira M, Karputs A, Kavaleuski A, Kuzminski I, Stepanova E, Gilep A. 2022. Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development. Applied Microbiology and Biotechnology. 106, 5093–5103.","apa":"Dormeshkin, D., Shapira, M., Karputs, A., Kavaleuski, A., Kuzminski, I., Stepanova, E., & Gilep, A. (2022). Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development. Applied Microbiology and Biotechnology. Springer Nature. https://doi.org/10.1007/s00253-022-12022-w","ieee":"D. Dormeshkin et al., “Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development,” Applied Microbiology and Biotechnology, vol. 106. Springer Nature, pp. 5093–5103, 2022.","mla":"Dormeshkin, Dmitri, et al. “Combining of Synthetic VHH and Immune ScFv Libraries for Pregnancy-Associated Glycoproteins ELISA Development.” Applied Microbiology and Biotechnology, vol. 106, Springer Nature, 2022, pp. 5093–103, doi:10.1007/s00253-022-12022-w.","short":"D. Dormeshkin, M. Shapira, A. Karputs, A. Kavaleuski, I. Kuzminski, E. Stepanova, A. Gilep, Applied Microbiology and Biotechnology 106 (2022) 5093–5103.","chicago":"Dormeshkin, Dmitri, Michail Shapira, Alena Karputs, Anton Kavaleuski, Ivan Kuzminski, Elena Stepanova, and Andrei Gilep. “Combining of Synthetic VHH and Immune ScFv Libraries for Pregnancy-Associated Glycoproteins ELISA Development.” Applied Microbiology and Biotechnology. Springer Nature, 2022. https://doi.org/10.1007/s00253-022-12022-w."},"publication":"Applied Microbiology and Biotechnology","date_published":"2022-08-01T00:00:00Z","scopus_import":"1","article_processing_charge":"No","day":"01"},{"doi":"10.1073/pnas.2020857118","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.2020857118"}],"external_id":{"isi":["000607270100073"],"pmid":["33443187"]},"quality_controlled":"1","isi":1,"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"}],"month":"01","publication_identifier":{"issn":["00278424"],"eissn":["10916490"]},"author":[{"first_name":"Lindy","last_name":"Abas","full_name":"Abas, Lindy"},{"last_name":"Kolb","first_name":"Martina","full_name":"Kolb, Martina"},{"full_name":"Stadlmann, Johannes","last_name":"Stadlmann","first_name":"Johannes"},{"last_name":"Janacek","first_name":"Dorina P.","full_name":"Janacek, Dorina P."},{"full_name":"Lukic, Kristina","last_name":"Lukic","first_name":"Kristina","orcid":"0000-0003-1581-881X","id":"2B04DB84-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schwechheimer, Claus","last_name":"Schwechheimer","first_name":"Claus"},{"full_name":"Sazanov, Leonid A","first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989"},{"full_name":"Mach, Lukas","last_name":"Mach","first_name":"Lukas"},{"last_name":"Friml","first_name":"Jiří","orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří"},{"full_name":"Hammes, Ulrich Z.","first_name":"Ulrich Z.","last_name":"Hammes"}],"related_material":{"link":[{"url":"https://doi.org/10.1073/pnas.2102232118","relation":"erratum"}]},"date_updated":"2023-08-07T13:29:23Z","date_created":"2021-01-03T23:01:23Z","volume":118,"year":"2021","acknowledgement":"This work was supported by Austrian Science Fund Grant FWF P21533-B20 (to L.A.); German Research Foundation Grant DFG HA3468/6-1 (to U.Z.H.); and European Research Council Grant 742985 (to J.F.). We thank Herta Steinkellner and Alexandra Castilho for N. benthamiana plants, Fabian Nagelreiter for statistical advice, Lanassa Bassukas for help with [ɣ32P]-\r\nATP assays, and Josef Penninger for providing access to mass spectrometry instruments at the Vienna BioCenter Core Facilities. We thank PNAS reviewers for the many comments and suggestions that helped to improve this manuscript.","pmid":1,"publication_status":"published","department":[{"_id":"JiFr"},{"_id":"LeSa"}],"publisher":"National Academy of Sciences","ec_funded":1,"article_number":"e2020857118","date_published":"2021-01-05T00:00:00Z","publication":"PNAS","citation":{"ama":"Abas L, Kolb M, Stadlmann J, et al. Naphthylphthalamic acid associates with and inhibits PIN auxin transporters. PNAS. 2021;118(1). doi:10.1073/pnas.2020857118","ista":"Abas L, Kolb M, Stadlmann J, Janacek DP, Lukic K, Schwechheimer C, Sazanov LA, Mach L, Friml J, Hammes UZ. 2021. Naphthylphthalamic acid associates with and inhibits PIN auxin transporters. PNAS. 118(1), e2020857118.","ieee":"L. Abas et al., “Naphthylphthalamic acid associates with and inhibits PIN auxin transporters,” PNAS, vol. 118, no. 1. National Academy of Sciences, 2021.","apa":"Abas, L., Kolb, M., Stadlmann, J., Janacek, D. P., Lukic, K., Schwechheimer, C., … Hammes, U. Z. (2021). Naphthylphthalamic acid associates with and inhibits PIN auxin transporters. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2020857118","mla":"Abas, Lindy, et al. “Naphthylphthalamic Acid Associates with and Inhibits PIN Auxin Transporters.” PNAS, vol. 118, no. 1, e2020857118, National Academy of Sciences, 2021, doi:10.1073/pnas.2020857118.","short":"L. Abas, M. Kolb, J. Stadlmann, D.P. Janacek, K. Lukic, C. Schwechheimer, L.A. Sazanov, L. Mach, J. Friml, U.Z. Hammes, PNAS 118 (2021).","chicago":"Abas, Lindy, Martina Kolb, Johannes Stadlmann, Dorina P. Janacek, Kristina Lukic, Claus Schwechheimer, Leonid A Sazanov, Lukas Mach, Jiří Friml, and Ulrich Z. Hammes. “Naphthylphthalamic Acid Associates with and Inhibits PIN Auxin Transporters.” PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2020857118."},"article_type":"original","day":"05","article_processing_charge":"No","scopus_import":"1","oa_version":"Published Version","_id":"8993","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Naphthylphthalamic acid associates with and inhibits PIN auxin transporters","status":"public","intvolume":" 118","abstract":[{"lang":"eng","text":"N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism."}],"issue":"1","type":"journal_article"},{"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"doi":"10.1016/j.isci.2021.102139","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000631646000012"],"pmid":["33665558"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"publication_identifier":{"eissn":["25890042"]},"month":"03","volume":24,"date_created":"2021-02-28T23:01:24Z","date_updated":"2023-08-07T13:54:06Z","author":[{"full_name":"Kampjut, Domen","first_name":"Domen","last_name":"Kampjut","id":"37233050-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Steiner, Julia","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Steiner"},{"last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A"}],"department":[{"_id":"LeSa"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"acknowledgement":"We thank the Electron Microscopy Facilities at the Institute of Science and Technology Austria and at the Vienna Biocenter for providing access and training for the electron microscopes. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement no. 665385 .","year":"2021","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"file_date_updated":"2021-03-03T07:38:14Z","article_number":"102139","date_published":"2021-03-19T00:00:00Z","article_type":"original","citation":{"ama":"Kampjut D, Steiner J, Sazanov LA. Cryo-EM grid optimization for membrane proteins. iScience. 2021;24(3). doi:10.1016/j.isci.2021.102139","ista":"Kampjut D, Steiner J, Sazanov LA. 2021. Cryo-EM grid optimization for membrane proteins. iScience. 24(3), 102139.","ieee":"D. Kampjut, J. Steiner, and L. A. Sazanov, “Cryo-EM grid optimization for membrane proteins,” iScience, vol. 24, no. 3. Elsevier, 2021.","apa":"Kampjut, D., Steiner, J., & Sazanov, L. A. (2021). Cryo-EM grid optimization for membrane proteins. IScience. Elsevier. https://doi.org/10.1016/j.isci.2021.102139","mla":"Kampjut, Domen, et al. “Cryo-EM Grid Optimization for Membrane Proteins.” IScience, vol. 24, no. 3, 102139, Elsevier, 2021, doi:10.1016/j.isci.2021.102139.","short":"D. Kampjut, J. Steiner, L.A. Sazanov, IScience 24 (2021).","chicago":"Kampjut, Domen, Julia Steiner, and Leonid A Sazanov. “Cryo-EM Grid Optimization for Membrane Proteins.” IScience. Elsevier, 2021. https://doi.org/10.1016/j.isci.2021.102139."},"publication":"iScience","has_accepted_license":"1","article_processing_charge":"No","day":"19","scopus_import":"1","file":[{"file_name":"2021_iScience_Kampjut.pdf","access_level":"open_access","creator":"dernst","file_size":7431411,"content_type":"application/pdf","file_id":"9219","relation":"main_file","date_created":"2021-03-03T07:38:14Z","date_updated":"2021-03-03T07:38:14Z","success":1,"checksum":"50585447386fe5842f07ab9b3a66e7e9"}],"oa_version":"Published Version","intvolume":" 24","status":"public","ddc":["570"],"title":"Cryo-EM grid optimization for membrane proteins","_id":"9205","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","issue":"3","abstract":[{"text":"Cryo-EM grid preparation is an important bottleneck in protein structure determination, especially for membrane proteins, typically requiring screening of a large number of conditions. We systematically investigated the effects of buffer components, blotting conditions and grid types on the outcome of grid preparation of five different membrane protein samples. Aggregation was the most common type of problem which was addressed by changing detergents, salt concentration or reconstitution of proteins into nanodiscs or amphipols. We show that the optimal concentration of detergent is between 0.05 and 0.4% and that the presence of a low concentration of detergent with a high critical micellar concentration protects the proteins from denaturation at the air-water interface. Furthermore, we discuss the strategies for achieving an adequate ice thickness, particle coverage and orientation distribution on free ice and on support films. Our findings provide a clear roadmap for comprehensive screening of conditions for cryo-EM grid preparation of membrane proteins.","lang":"eng"}],"type":"journal_article"},{"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"month":"10","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"ScienComp"}],"doi":"10.1038/s41586-021-03927-z","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"}],"quality_controlled":"1","isi":1,"external_id":{"pmid":["34616041"],"isi":["000704581600001"]},"ec_funded":1,"volume":598,"date_created":"2021-10-17T22:01:17Z","date_updated":"2023-08-14T08:01:21Z","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boosting-the-cells-power-house/","relation":"press_release","description":"News on IST Webpage"}]},"author":[{"orcid":"0000-0001-5618-3449","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","last_name":"Vercellino","first_name":"Irene","full_name":"Vercellino, Irene"},{"first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"department":[{"_id":"LeSa"}],"publisher":"Springer Nature","publication_status":"published","pmid":1,"acknowledgement":"We thank the pre-clinical facility of the IST Austria and A. Venturino for assistance with the animals; and V.-V. Hodirnau for assistance during the Titan Krios data collection, performed at the IST Austria. The data processing was performed at the IST high-performance computing cluster. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754411.","year":"2021","article_processing_charge":"No","day":"14","scopus_import":"1","date_published":"2021-10-14T00:00:00Z","page":"364-367","article_type":"original","citation":{"ama":"Vercellino I, Sazanov LA. Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature. 2021;598(7880):364-367. doi:10.1038/s41586-021-03927-z","ieee":"I. Vercellino and L. A. Sazanov, “Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV,” Nature, vol. 598, no. 7880. Springer Nature, pp. 364–367, 2021.","apa":"Vercellino, I., & Sazanov, L. A. (2021). Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature. Springer Nature. https://doi.org/10.1038/s41586-021-03927-z","ista":"Vercellino I, Sazanov LA. 2021. Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature. 598(7880), 364–367.","short":"I. Vercellino, L.A. Sazanov, Nature 598 (2021) 364–367.","mla":"Vercellino, Irene, and Leonid A. Sazanov. “Structure and Assembly of the Mammalian Mitochondrial Supercomplex CIII2CIV.” Nature, vol. 598, no. 7880, Springer Nature, 2021, pp. 364–67, doi:10.1038/s41586-021-03927-z.","chicago":"Vercellino, Irene, and Leonid A Sazanov. “Structure and Assembly of the Mammalian Mitochondrial Supercomplex CIII2CIV.” Nature. Springer Nature, 2021. https://doi.org/10.1038/s41586-021-03927-z."},"publication":"Nature","issue":"7880","abstract":[{"text":"The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain.","lang":"eng"}],"type":"journal_article","oa_version":"None","intvolume":" 598","title":"Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV","status":"public","_id":"10146","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"publication_status":"published","publisher":"Springer ","department":[{"_id":"LeSa"}],"year":"2021","acknowledgement":"We are grateful for additional support and valuable scientific input for this project by Yuko Misumi, Jiannan Li, Hisako Kubota-Kawai, Takeshi Kawabata, Mian Wu, Eiki Yamashita, Atsushi Nakagawa, Volker Hartmann, Melanie Völkel and Matthias Rögner. Parts of this research were funded by the German Research Council (DFG) within the framework of GRK 2341 (Microbial Substrate Conversion) to M.M.N., the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED under grant number JP20am0101117 (K.N.), JP16K07266 to Atsunori Oshima and C.G., a Grants-in-Aid for Scientific Research under grant number JP 25000013 (K.N.), 17H03647 (C.G.) and 16H06560 (G.K.) from MEXT-KAKENHI, the International Joint Research Promotion Program from Osaka University to M.M.N., C.G. and G.K., and the Cyclic Innovation for Clinical Empowerment (CiCLE) Grant Number JP17pc0101020 from AMED to K.N. and G.K.","pmid":1,"date_created":"2021-11-19T11:37:29Z","date_updated":"2023-08-14T11:51:19Z","volume":4,"author":[{"full_name":"Çoruh, Mehmet Orkun","id":"d25163e5-8d53-11eb-a251-e6dd8ea1b8ef","orcid":"0000-0002-3219-2022","first_name":"Mehmet Orkun","last_name":"Çoruh"},{"first_name":"Anna","last_name":"Frank","full_name":"Frank, Anna"},{"first_name":"Hideaki","last_name":"Tanaka","full_name":"Tanaka, Hideaki"},{"full_name":"Kawamoto, Akihiro","last_name":"Kawamoto","first_name":"Akihiro"},{"last_name":"El-Mohsnawy","first_name":"Eithar","full_name":"El-Mohsnawy, Eithar"},{"first_name":"Takayuki","last_name":"Kato","full_name":"Kato, Takayuki"},{"first_name":"Keiichi","last_name":"Namba","full_name":"Namba, Keiichi"},{"last_name":"Gerle","first_name":"Christoph","full_name":"Gerle, Christoph"},{"full_name":"Nowaczyk, Marc M.","first_name":"Marc M.","last_name":"Nowaczyk"},{"last_name":"Kurisu","first_name":"Genji","full_name":"Kurisu, Genji"}],"article_number":"304","file_date_updated":"2021-11-19T15:09:18Z","quality_controlled":"1","isi":1,"external_id":{"isi":["000627440700001"],"pmid":["33686186"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1038/s42003-021-01808-9","month":"03","publication_identifier":{"issn":["2399-3642"]},"title":"Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster","ddc":["570"],"status":"public","intvolume":" 4","_id":"10310","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"checksum":"8ffd39f2bba7152a2441802ff313bf0b","success":1,"date_updated":"2021-11-19T15:09:18Z","date_created":"2021-11-19T15:09:18Z","relation":"main_file","file_id":"10318","content_type":"application/pdf","file_size":6030261,"creator":"cchlebak","access_level":"open_access","file_name":"2021_CommBio_Çoruh.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700."}],"issue":"1","article_type":"original","publication":"Communications Biology","citation":{"chicago":"Çoruh, Mehmet Orkun, Anna Frank, Hideaki Tanaka, Akihiro Kawamoto, Eithar El-Mohsnawy, Takayuki Kato, Keiichi Namba, Christoph Gerle, Marc M. Nowaczyk, and Genji Kurisu. “Cryo-EM Structure of a Functional Monomeric Photosystem I from Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications Biology. Springer , 2021. https://doi.org/10.1038/s42003-021-01808-9.","short":"M.O. Çoruh, A. Frank, H. Tanaka, A. Kawamoto, E. El-Mohsnawy, T. Kato, K. Namba, C. Gerle, M.M. Nowaczyk, G. Kurisu, Communications Biology 4 (2021).","mla":"Çoruh, Mehmet Orkun, et al. “Cryo-EM Structure of a Functional Monomeric Photosystem I from Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications Biology, vol. 4, no. 1, 304, Springer , 2021, doi:10.1038/s42003-021-01808-9.","ieee":"M. O. Çoruh et al., “Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster,” Communications Biology, vol. 4, no. 1. Springer , 2021.","apa":"Çoruh, M. O., Frank, A., Tanaka, H., Kawamoto, A., El-Mohsnawy, E., Kato, T., … Kurisu, G. (2021). Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications Biology. Springer . https://doi.org/10.1038/s42003-021-01808-9","ista":"Çoruh MO, Frank A, Tanaka H, Kawamoto A, El-Mohsnawy E, Kato T, Namba K, Gerle C, Nowaczyk MM, Kurisu G. 2021. Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications Biology. 4(1), 304.","ama":"Çoruh MO, Frank A, Tanaka H, et al. Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications Biology. 2021;4(1). doi:10.1038/s42003-021-01808-9"},"date_published":"2021-03-08T00:00:00Z","keyword":["general agricultural and biological Sciences","general biochemistry","genetics and molecular biology","medicine (miscellaneous)"],"scopus_import":"1","day":"08","has_accepted_license":"1","article_processing_charge":"No"},{"language":[{"iso":"eng"}],"doi":"10.1016/j.bbabio.2020.148213","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["32335026"],"isi":["000540842000012"]},"publication_identifier":{"issn":["00052728"],"eissn":["18792650"]},"month":"08","volume":1861,"date_updated":"2023-08-21T06:19:18Z","date_created":"2020-05-03T22:00:47Z","author":[{"full_name":"Adjobo-Hermans, Merel J.W.","last_name":"Adjobo-Hermans","first_name":"Merel J.W."},{"full_name":"De Haas, Ria","first_name":"Ria","last_name":"De Haas"},{"full_name":"Willems, Peter H.G.M.","last_name":"Willems","first_name":"Peter H.G.M."},{"full_name":"Wojtala, Aleksandra","last_name":"Wojtala","first_name":"Aleksandra"},{"first_name":"Sjenet E.","last_name":"Van Emst-De Vries","full_name":"Van Emst-De Vries, Sjenet E."},{"last_name":"Wagenaars","first_name":"Jori A.","full_name":"Wagenaars, Jori A."},{"full_name":"Van Den Brand, Mariel","first_name":"Mariel","last_name":"Van Den Brand"},{"full_name":"Rodenburg, Richard J.","last_name":"Rodenburg","first_name":"Richard J."},{"full_name":"Smeitink, Jan A.M.","last_name":"Smeitink","first_name":"Jan A.M."},{"first_name":"Leo G.","last_name":"Nijtmans","full_name":"Nijtmans, Leo G."},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A","last_name":"Sazanov","full_name":"Sazanov, Leonid A"},{"last_name":"Wieckowski","first_name":"Mariusz R.","full_name":"Wieckowski, Mariusz R."},{"full_name":"Koopman, Werner J.H.","last_name":"Koopman","first_name":"Werner J.H."}],"publisher":"Elsevier","department":[{"_id":"LeSa"}],"publication_status":"published","pmid":1,"year":"2020","file_date_updated":"2020-07-14T12:48:03Z","article_number":"148213","date_published":"2020-08-01T00:00:00Z","article_type":"original","citation":{"ama":"Adjobo-Hermans MJW, De Haas R, Willems PHGM, et al. NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2. Biochimica et Biophysica Acta - Bioenergetics. 2020;1861(8). doi:10.1016/j.bbabio.2020.148213","ista":"Adjobo-Hermans MJW, De Haas R, Willems PHGM, Wojtala A, Van Emst-De Vries SE, Wagenaars JA, Van Den Brand M, Rodenburg RJ, Smeitink JAM, Nijtmans LG, Sazanov LA, Wieckowski MR, Koopman WJH. 2020. NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2. Biochimica et Biophysica Acta - Bioenergetics. 1861(8), 148213.","ieee":"M. J. W. Adjobo-Hermans et al., “NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1861, no. 8. Elsevier, 2020.","apa":"Adjobo-Hermans, M. J. W., De Haas, R., Willems, P. H. G. M., Wojtala, A., Van Emst-De Vries, S. E., Wagenaars, J. A., … Koopman, W. J. H. (2020). NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2. Biochimica et Biophysica Acta - Bioenergetics. Elsevier. https://doi.org/10.1016/j.bbabio.2020.148213","mla":"Adjobo-Hermans, Merel J. W., et al. “NDUFS4 Deletion Triggers Loss of NDUFA12 in Ndufs4−/− Mice and Leigh Syndrome Patients: A Stabilizing Role for NDUFAF2.” Biochimica et Biophysica Acta - Bioenergetics, vol. 1861, no. 8, 148213, Elsevier, 2020, doi:10.1016/j.bbabio.2020.148213.","short":"M.J.W. Adjobo-Hermans, R. De Haas, P.H.G.M. Willems, A. Wojtala, S.E. Van Emst-De Vries, J.A. Wagenaars, M. Van Den Brand, R.J. Rodenburg, J.A.M. Smeitink, L.G. Nijtmans, L.A. Sazanov, M.R. Wieckowski, W.J.H. Koopman, Biochimica et Biophysica Acta - Bioenergetics 1861 (2020).","chicago":"Adjobo-Hermans, Merel J.W., Ria De Haas, Peter H.G.M. Willems, Aleksandra Wojtala, Sjenet E. Van Emst-De Vries, Jori A. Wagenaars, Mariel Van Den Brand, et al. “NDUFS4 Deletion Triggers Loss of NDUFA12 in Ndufs4−/− Mice and Leigh Syndrome Patients: A Stabilizing Role for NDUFAF2.” Biochimica et Biophysica Acta - Bioenergetics. Elsevier, 2020. https://doi.org/10.1016/j.bbabio.2020.148213."},"publication":"Biochimica et Biophysica Acta - Bioenergetics","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1","oa_version":"Published Version","file":[{"file_id":"7798","relation":"main_file","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-04T12:25:19Z","checksum":"a9b152381307cf45fe266a8dc5640388","file_name":"2020_BBA_Adjobo_Hermans.pdf","access_level":"open_access","creator":"dernst","file_size":3826792,"content_type":"application/pdf"}],"intvolume":" 1861","title":"NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2","ddc":["570"],"status":"public","_id":"7788","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","issue":"8","abstract":[{"lang":"eng","text":"Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly understood pediatric disorder featuring brain-specific anomalies and early death. To study the LS pathomechanism, we here compared OXPHOS proteomes between various Ndufs4−/− mouse tissues. Ndufs4−/− animals displayed significantly lower CI subunit levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4 induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction in other CI subunit levels, and an increase in specific CI assembly factors. Among the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2, identical results were obtained in Ndufs4−/− mouse embryonic fibroblasts (MEFs) and NDUFS4-mutated LS patient cells. Ndufs4−/− MEFs contained active CI in situ but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex (CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells, NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830 (NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological and CI in silico structural analysis, we conclude that absence of NDUFS4 induces near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes active CI in Ndufs4−/− mice and LS patient cells, perhaps in concert with mitochondrial inner membrane lipids."}],"type":"journal_article"},{"pmid":1,"year":"2020","publisher":"American Chemical Society","department":[{"_id":"LeSa"}],"publication_status":"published","related_material":{"record":[{"relation":"research_data","status":"public","id":"9326"},{"id":"9713","relation":"research_data","status":"public"},{"relation":"research_data","status":"public","id":"9878"}]},"author":[{"full_name":"Gupta, Chitrak","last_name":"Gupta","first_name":"Chitrak"},{"full_name":"Khaniya, Umesh","first_name":"Umesh","last_name":"Khaniya"},{"first_name":"Chun Kit","last_name":"Chan","full_name":"Chan, Chun Kit"},{"full_name":"Dehez, Francois","first_name":"Francois","last_name":"Dehez"},{"first_name":"Mrinal","last_name":"Shekhar","full_name":"Shekhar, Mrinal"},{"full_name":"Gunner, M. R.","last_name":"Gunner","first_name":"M. R."},{"last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A"},{"last_name":"Chipot","first_name":"Christophe","full_name":"Chipot, Christophe"},{"full_name":"Singharoy, Abhishek","first_name":"Abhishek","last_name":"Singharoy"}],"volume":142,"date_updated":"2023-08-22T07:49:38Z","date_created":"2020-06-29T07:59:35Z","external_id":{"pmid":["32347721"],"isi":["000537415600020"]},"isi":1,"quality_controlled":"1","doi":"10.1021/jacs.9b13450","language":[{"iso":"eng"}],"publication_identifier":{"issn":["00027863"],"eissn":["15205126"]},"month":"05","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8040","intvolume":" 142","title":"Charge transfer and chemo-mechanical coupling in respiratory complex I","status":"public","oa_version":"None","type":"journal_article","issue":"20","abstract":[{"text":"The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol form—a design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.","lang":"eng"}],"citation":{"ama":"Gupta C, Khaniya U, Chan CK, et al. Charge transfer and chemo-mechanical coupling in respiratory complex I. Journal of the American Chemical Society. 2020;142(20):9220-9230. doi:10.1021/jacs.9b13450","ista":"Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Charge transfer and chemo-mechanical coupling in respiratory complex I. Journal of the American Chemical Society. 142(20), 9220–9230.","apa":"Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Charge transfer and chemo-mechanical coupling in respiratory complex I. Journal of the American Chemical Society. American Chemical Society. https://doi.org/10.1021/jacs.9b13450","ieee":"C. Gupta et al., “Charge transfer and chemo-mechanical coupling in respiratory complex I,” Journal of the American Chemical Society, vol. 142, no. 20. American Chemical Society, pp. 9220–9230, 2020.","mla":"Gupta, Chitrak, et al. “Charge Transfer and Chemo-Mechanical Coupling in Respiratory Complex I.” Journal of the American Chemical Society, vol. 142, no. 20, American Chemical Society, 2020, pp. 9220–30, doi:10.1021/jacs.9b13450.","short":"C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, Journal of the American Chemical Society 142 (2020) 9220–9230.","chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar, M. R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Charge Transfer and Chemo-Mechanical Coupling in Respiratory Complex I.” Journal of the American Chemical Society. American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450."},"publication":"Journal of the American Chemical Society","page":"9220-9230","article_type":"original","date_published":"2020-05-20T00:00:00Z","scopus_import":"1","article_processing_charge":"No","day":"20"},{"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"8040"}]},"author":[{"full_name":"Gupta, Chitrak","first_name":"Chitrak","last_name":"Gupta"},{"last_name":"Khaniya","first_name":"Umesh","full_name":"Khaniya, Umesh"},{"last_name":"Chan","first_name":"Chun","full_name":"Chan, Chun"},{"full_name":"Dehez, Francois","last_name":"Dehez","first_name":"Francois"},{"full_name":"Shekhar, Mrinal","last_name":"Shekhar","first_name":"Mrinal"},{"last_name":"Gunner","first_name":"M. R.","full_name":"Gunner, M. R."},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A","last_name":"Sazanov","full_name":"Sazanov, Leonid A"},{"last_name":"Chipot","first_name":"Christophe","full_name":"Chipot, Christophe"},{"last_name":"Singharoy","first_name":"Abhishek","full_name":"Singharoy, Abhishek"}],"oa_version":"Published Version","date_updated":"2023-08-22T07:49:37Z","date_created":"2021-04-14T12:05:20Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"9326","year":"2020","department":[{"_id":"LeSa"}],"publisher":"American Chemical Society","status":"public","title":"Charge transfer and chemo-mechanical coupling in respiratory complex I","abstract":[{"text":"The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol forma design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.","lang":"eng"}],"license":"https://creativecommons.org/licenses/by-nc/4.0/","type":"research_data_reference","doi":"10.1021/jacs.9b13450.s002","date_published":"2020-05-20T00:00:00Z","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"oa":1,"citation":{"chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Chan, Francois Dehez, Mrinal Shekhar, M. R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Charge Transfer and Chemo-Mechanical Coupling in Respiratory Complex I.” American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450.s002.","mla":"Gupta, Chitrak, et al. Charge Transfer and Chemo-Mechanical Coupling in Respiratory Complex I. American Chemical Society, 2020, doi:10.1021/jacs.9b13450.s002.","short":"C. Gupta, U. Khaniya, C. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, (2020).","ista":"Gupta C, Khaniya U, Chan C, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Charge transfer and chemo-mechanical coupling in respiratory complex I, American Chemical Society, 10.1021/jacs.9b13450.s002.","apa":"Gupta, C., Khaniya, U., Chan, C., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Charge transfer and chemo-mechanical coupling in respiratory complex I. American Chemical Society. https://doi.org/10.1021/jacs.9b13450.s002","ieee":"C. Gupta et al., “Charge transfer and chemo-mechanical coupling in respiratory complex I.” American Chemical Society, 2020.","ama":"Gupta C, Khaniya U, Chan C, et al. Charge transfer and chemo-mechanical coupling in respiratory complex I. 2020. doi:10.1021/jacs.9b13450.s002"},"main_file_link":[{"open_access":"1"}],"article_processing_charge":"No","day":"20","month":"05"},{"citation":{"chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar, M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Supporting Information.” American Chemical Society , 2020. https://doi.org/10.1021/jacs.9b13450.s001.","mla":"Gupta, Chitrak, et al. Supporting Information. American Chemical Society , 2020, doi:10.1021/jacs.9b13450.s001.","short":"C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, (2020).","ista":"Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Supporting information, American Chemical Society , 10.1021/jacs.9b13450.s001.","apa":"Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Supporting information. American Chemical Society . https://doi.org/10.1021/jacs.9b13450.s001","ieee":"C. Gupta et al., “Supporting information.” American Chemical Society , 2020.","ama":"Gupta C, Khaniya U, Chan CK, et al. Supporting information. 2020. doi:10.1021/jacs.9b13450.s001"},"doi":"10.1021/jacs.9b13450.s001","date_published":"2020-05-20T00:00:00Z","article_processing_charge":"No","day":"20","month":"05","department":[{"_id":"LeSa"}],"publisher":"American Chemical Society ","status":"public","title":"Supporting information","_id":"9713","year":"2020","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version","date_created":"2021-07-23T12:02:39Z","date_updated":"2023-08-22T07:49:38Z","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"8040"}]},"author":[{"last_name":"Gupta","first_name":"Chitrak","full_name":"Gupta, Chitrak"},{"first_name":"Umesh","last_name":"Khaniya","full_name":"Khaniya, Umesh"},{"full_name":"Chan, Chun Kit","last_name":"Chan","first_name":"Chun Kit"},{"first_name":"Francois","last_name":"Dehez","full_name":"Dehez, Francois"},{"last_name":"Shekhar","first_name":"Mrinal","full_name":"Shekhar, Mrinal"},{"first_name":"M.R.","last_name":"Gunner","full_name":"Gunner, M.R."},{"first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"},{"full_name":"Chipot, Christophe","last_name":"Chipot","first_name":"Christophe"},{"first_name":"Abhishek","last_name":"Singharoy","full_name":"Singharoy, Abhishek"}],"type":"research_data_reference","abstract":[{"text":"Additional analyses of the trajectories","lang":"eng"}]},{"citation":{"ama":"Gupta C, Khaniya U, Chan CK, et al. Movies. 2020. doi:10.1021/jacs.9b13450.s002","ieee":"C. Gupta et al., “Movies.” American Chemical Society, 2020.","apa":"Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Movies. American Chemical Society. https://doi.org/10.1021/jacs.9b13450.s002","ista":"Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Movies, American Chemical Society, 10.1021/jacs.9b13450.s002.","short":"C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, (2020).","mla":"Gupta, Chitrak, et al. Movies. American Chemical Society, 2020, doi:10.1021/jacs.9b13450.s002.","chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar, M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Movies.” American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450.s002."},"date_published":"2020-05-20T00:00:00Z","doi":"10.1021/jacs.9b13450.s002","day":"20","month":"05","article_processing_charge":"No","title":"Movies","status":"public","department":[{"_id":"LeSa"}],"publisher":"American Chemical Society","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9878","year":"2020","date_updated":"2023-08-22T07:49:38Z","date_created":"2021-08-11T09:18:54Z","oa_version":"Published Version","author":[{"last_name":"Gupta","first_name":"Chitrak","full_name":"Gupta, Chitrak"},{"last_name":"Khaniya","first_name":"Umesh","full_name":"Khaniya, Umesh"},{"full_name":"Chan, Chun Kit","last_name":"Chan","first_name":"Chun Kit"},{"first_name":"Francois","last_name":"Dehez","full_name":"Dehez, Francois"},{"full_name":"Shekhar, Mrinal","last_name":"Shekhar","first_name":"Mrinal"},{"full_name":"Gunner, M.R.","first_name":"M.R.","last_name":"Gunner"},{"full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A","last_name":"Sazanov"},{"last_name":"Chipot","first_name":"Christophe","full_name":"Chipot, Christophe"},{"full_name":"Singharoy, Abhishek","first_name":"Abhishek","last_name":"Singharoy"}],"related_material":{"record":[{"id":"8040","status":"public","relation":"used_in_publication"}]},"type":"research_data_reference"},{"day":"18","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2020-08-18T00:00:00Z","article_type":"original","publication":"Nature Communications","citation":{"chicago":"Gutierrez-Fernandez, Javier, Karol Kaszuba, Gurdeep S. Minhas, Rozbeh Baradaran, Margherita Tambalo, David T. Gallagher, and Leonid A Sazanov. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17957-0.","mla":"Gutierrez-Fernandez, Javier, et al. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications, vol. 11, no. 1, 4135, Springer Nature, 2020, doi:10.1038/s41467-020-17957-0.","short":"J. Gutierrez-Fernandez, K. Kaszuba, G.S. Minhas, R. Baradaran, M. Tambalo, D.T. Gallagher, L.A. Sazanov, Nature Communications 11 (2020).","ista":"Gutierrez-Fernandez J, Kaszuba K, Minhas GS, Baradaran R, Tambalo M, Gallagher DT, Sazanov LA. 2020. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 11(1), 4135.","ieee":"J. Gutierrez-Fernandez et al., “Key role of quinone in the mechanism of respiratory complex I,” Nature Communications, vol. 11, no. 1. Springer Nature, 2020.","apa":"Gutierrez-Fernandez, J., Kaszuba, K., Minhas, G. S., Baradaran, R., Tambalo, M., Gallagher, D. T., & Sazanov, L. A. (2020). Key role of quinone in the mechanism of respiratory complex I. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17957-0","ama":"Gutierrez-Fernandez J, Kaszuba K, Minhas GS, et al. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 2020;11(1). doi:10.1038/s41467-020-17957-0"},"abstract":[{"lang":"eng","text":"Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I."}],"issue":"1","type":"journal_article","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"8326","checksum":"52b96f41d7d0db9728064c08da00d030","success":1,"date_updated":"2020-08-31T13:40:00Z","date_created":"2020-08-31T13:40:00Z","access_level":"open_access","file_name":"2020_NatComm_Gutierrez-Fernandez.pdf","file_size":7527373,"content_type":"application/pdf","creator":"cziletti"}],"title":"Key role of quinone in the mechanism of respiratory complex I","status":"public","ddc":["570"],"intvolume":" 11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8318","month":"08","publication_identifier":{"eissn":["20411723"]},"language":[{"iso":"eng"}],"doi":"10.1038/s41467-020-17957-0","isi":1,"quality_controlled":"1","external_id":{"pmid":["32811817"],"isi":["000607072900001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"file_date_updated":"2020-08-31T13:40:00Z","article_number":"4135","date_updated":"2023-08-22T09:03:00Z","date_created":"2020-08-30T22:01:10Z","volume":11,"author":[{"first_name":"Javier","last_name":"Gutierrez-Fernandez","id":"3D9511BA-F248-11E8-B48F-1D18A9856A87","full_name":"Gutierrez-Fernandez, Javier"},{"last_name":"Kaszuba","first_name":"Karol","id":"3FDF9472-F248-11E8-B48F-1D18A9856A87","full_name":"Kaszuba, Karol"},{"first_name":"Gurdeep S.","last_name":"Minhas","full_name":"Minhas, Gurdeep S."},{"last_name":"Baradaran","first_name":"Rozbeh","full_name":"Baradaran, Rozbeh"},{"full_name":"Tambalo, Margherita","last_name":"Tambalo","first_name":"Margherita","id":"4187dfe4-ec23-11ea-ae46-f08ab378313a"},{"full_name":"Gallagher, David T.","first_name":"David T.","last_name":"Gallagher"},{"full_name":"Sazanov, Leonid A","first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/","description":"News on IST Homepage","relation":"press_release"}]},"publication_status":"published","department":[{"_id":"LeSa"}],"publisher":"Springer Nature","acknowledgement":"This work was funded by the Medical Research Council, UK and IST Austria. We thank the European Synchrotron Radiation Facility and the Diamond Light Source for provision of synchrotron radiation facilities. We are grateful to the staff of beamlines ID29, ID23-2 (ESRF, Grenoble, France) and I03 (Diamond Light Source, Didcot, UK) for assistance. Data processing was performed at the IST high-performance computing cluster.","year":"2020","pmid":1},{"doi":"10.3390/membranes10090242","language":[{"iso":"eng"}],"external_id":{"isi":["000581446000001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","isi":1,"month":"09","publication_identifier":{"eissn":["20770375"]},"author":[{"full_name":"Andrei, Andreea","first_name":"Andreea","last_name":"Andrei"},{"first_name":"Yavuz","last_name":"Öztürk","full_name":"Öztürk, Yavuz"},{"full_name":"Khalfaoui-Hassani, Bahia","last_name":"Khalfaoui-Hassani","first_name":"Bahia"},{"full_name":"Rauch, Juna","last_name":"Rauch","first_name":"Juna"},{"full_name":"Marckmann, Dorian","first_name":"Dorian","last_name":"Marckmann"},{"full_name":"Trasnea, Petru Iulian","id":"D560034C-10C4-11EA-ABF4-A4B43DDC885E","first_name":"Petru Iulian","last_name":"Trasnea"},{"full_name":"Daldal, Fevzi","first_name":"Fevzi","last_name":"Daldal"},{"full_name":"Koch, Hans-Georg","last_name":"Koch","first_name":"Hans-Georg"}],"date_updated":"2023-08-22T09:34:06Z","date_created":"2020-09-28T08:59:26Z","volume":10,"year":"2020","publication_status":"published","publisher":"MDPI","department":[{"_id":"LeSa"}],"file_date_updated":"2020-09-28T11:36:50Z","article_number":"242","date_published":"2020-09-01T00:00:00Z","publication":"Membranes","citation":{"ieee":"A. Andrei et al., “Cu homeostasis in bacteria: The ins and outs,” Membranes, vol. 10, no. 9. MDPI, 2020.","apa":"Andrei, A., Öztürk, Y., Khalfaoui-Hassani, B., Rauch, J., Marckmann, D., Trasnea, P. I., … Koch, H.-G. (2020). Cu homeostasis in bacteria: The ins and outs. Membranes. MDPI. https://doi.org/10.3390/membranes10090242","ista":"Andrei A, Öztürk Y, Khalfaoui-Hassani B, Rauch J, Marckmann D, Trasnea PI, Daldal F, Koch H-G. 2020. Cu homeostasis in bacteria: The ins and outs. Membranes. 10(9), 242.","ama":"Andrei A, Öztürk Y, Khalfaoui-Hassani B, et al. Cu homeostasis in bacteria: The ins and outs. Membranes. 2020;10(9). doi:10.3390/membranes10090242","chicago":"Andrei, Andreea, Yavuz Öztürk, Bahia Khalfaoui-Hassani, Juna Rauch, Dorian Marckmann, Petru Iulian Trasnea, Fevzi Daldal, and Hans-Georg Koch. “Cu Homeostasis in Bacteria: The Ins and Outs.” Membranes. MDPI, 2020. https://doi.org/10.3390/membranes10090242.","short":"A. Andrei, Y. Öztürk, B. Khalfaoui-Hassani, J. Rauch, D. Marckmann, P.I. Trasnea, F. Daldal, H.-G. Koch, Membranes 10 (2020).","mla":"Andrei, Andreea, et al. “Cu Homeostasis in Bacteria: The Ins and Outs.” Membranes, vol. 10, no. 9, 242, MDPI, 2020, doi:10.3390/membranes10090242."},"article_type":"original","day":"01","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","file":[{"file_name":"2020_Membranes_Andrei.pdf","access_level":"open_access","content_type":"application/pdf","file_size":4612258,"creator":"dernst","relation":"main_file","file_id":"8583","date_updated":"2020-09-28T11:36:50Z","date_created":"2020-09-28T11:36:50Z","checksum":"ceb43d7554e712dea6f36f9287271737","success":1}],"oa_version":"Published Version","_id":"8579","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","ddc":["570"],"title":"Cu homeostasis in bacteria: The ins and outs","intvolume":" 10","abstract":[{"lang":"eng","text":"Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells."}],"issue":"9","type":"journal_article"},{"month":"11","publication_identifier":{"eissn":["15459985"],"issn":["15459993"]},"quality_controlled":"1","isi":1,"external_id":{"isi":["000569299400004"],"pmid":["32929284"]},"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"ScienComp"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41594-020-0503-8","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"LeSa"}],"acknowledgement":"We thank J. Novacek from CEITEC (Brno, Czech Republic) for assistance with collecting the FEI Krios dataset and iNEXT for providing access to CEITEC. We thank the IST Austria EM facility for access and assistance with collecting the FEI Glacios dataset. Data processing was performed at the IST high-performance computing cluster. This work has been supported by iNEXT EM HEDC (proposal 4506), funded by the Horizon 2020 Programme of the European Commission.","year":"2020","pmid":1,"date_updated":"2023-08-22T09:33:09Z","date_created":"2020-09-28T08:59:27Z","volume":27,"author":[{"first_name":"Gergely","last_name":"Pinke","id":"4D5303E6-F248-11E8-B48F-1D18A9856A87","full_name":"Pinke, Gergely"},{"full_name":"Zhou, Long","orcid":"0000-0002-1864-8951","id":"3E751364-F248-11E8-B48F-1D18A9856A87","last_name":"Zhou","first_name":"Long"},{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","first_name":"Leonid A"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/structure-of-atpase-solved/","relation":"press_release","description":"News on IST Homepage"}]},"scopus_import":"1","day":"01","article_processing_charge":"No","article_type":"original","page":"1077-1085","publication":"Nature Structural and Molecular Biology","citation":{"ista":"Pinke G, Zhou L, Sazanov LA. 2020. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 27(11), 1077–1085.","apa":"Pinke, G., Zhou, L., & Sazanov, L. A. (2020). Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-020-0503-8","ieee":"G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian F-type ATP synthase,” Nature Structural and Molecular Biology, vol. 27, no. 11. Springer Nature, pp. 1077–1085, 2020.","ama":"Pinke G, Zhou L, Sazanov LA. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 2020;27(11):1077-1085. doi:10.1038/s41594-020-0503-8","chicago":"Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology. Springer Nature, 2020. https://doi.org/10.1038/s41594-020-0503-8.","mla":"Pinke, Gergely, et al. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology, vol. 27, no. 11, Springer Nature, 2020, pp. 1077–85, doi:10.1038/s41594-020-0503-8.","short":"G. Pinke, L. Zhou, L.A. Sazanov, Nature Structural and Molecular Biology 27 (2020) 1077–1085."},"date_published":"2020-11-01T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant ‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine."}],"issue":"11","status":"public","title":"Cryo-EM structure of the entire mammalian F-type ATP synthase","intvolume":" 27","_id":"8581","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None"}]