[{"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"eissn":["1470-8728"],"issn":["0264-6021"]},"license":"https://creativecommons.org/licenses/by/4.0/","volume":480,"issue":"5","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally the entire complex from Thermus thermophilus. The developments in cryo-EM technology allowed us to solve the first complete structure of the twice larger, ∼1 MDa mammalian enzyme in 2016. However, the mechanism coupling, over large distances, the transfer of two electrons to pumping of four protons across the membrane remained an enigma. Recently we have solved high-resolution structures of mammalian and bacterial complex I under a range of redox conditions, including catalytic turnover. This allowed us to propose a robust and universal mechanism for complex I and related protein families. Redox reactions initially drive conformational changes around the quinone cavity and a long-distance transfer of substrate protons. These set up a stage for a series of electrostatically driven proton transfers along the membrane arm (‘domino effect'), eventually resulting in proton expulsion from the distal antiporter-like subunit. The mechanism radically differs from previous suggestions, however, it naturally explains all the unusual structural features of complex I. In this review I discuss the state of knowledge on complex I, including the current most controversial issues."}],"intvolume":" 480","month":"03","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1042/BCJ20210285"}],"scopus_import":"1","ddc":["570"],"date_updated":"2023-08-01T13:45:12Z","department":[{"_id":"LeSa"}],"_id":"12757","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"review","type":"journal_article","publication":"The Biochemical Journal","day":"15","year":"2023","has_accepted_license":"1","isi":1,"date_created":"2023-03-26T22:01:06Z","date_published":"2023-03-15T00:00:00Z","doi":"10.1042/BCJ20210285","page":"319-333","oa":1,"quality_controlled":"1","publisher":"Portland Press","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Sazanov LA. 2023. From the ‘black box’ to ‘domino effect’ mechanism: What have we learned from the structures of respiratory complex I. The Biochemical Journal. 480(5), 319–333.","chicago":"Sazanov, Leonid A. “From the ‘black Box’ to ‘Domino Effect’ Mechanism: What Have We Learned from the Structures of Respiratory Complex I.” The Biochemical Journal. Portland Press, 2023. https://doi.org/10.1042/BCJ20210285.","short":"L.A. Sazanov, The Biochemical Journal 480 (2023) 319–333.","ieee":"L. A. Sazanov, “From the ‘black box’ to ‘domino effect’ mechanism: What have we learned from the structures of respiratory complex I,” The Biochemical Journal, vol. 480, no. 5. Portland Press, pp. 319–333, 2023.","ama":"Sazanov LA. From the “black box” to “domino effect” mechanism: What have we learned from the structures of respiratory complex I. The Biochemical Journal. 2023;480(5):319-333. doi:10.1042/BCJ20210285","apa":"Sazanov, L. A. (2023). From the “black box” to “domino effect” mechanism: What have we learned from the structures of respiratory complex I. The Biochemical Journal. Portland Press. https://doi.org/10.1042/BCJ20210285","mla":"Sazanov, Leonid A. “From the ‘black Box’ to ‘Domino Effect’ Mechanism: What Have We Learned from the Structures of Respiratory Complex I.” The Biochemical Journal, vol. 480, no. 5, Portland Press, 2023, pp. 319–33, doi:10.1042/BCJ20210285."},"title":"From the 'black box' to 'domino effect' mechanism: What have we learned from the structures of respiratory complex I","external_id":{"pmid":["36920092"],"isi":["000957065700001"]},"article_processing_charge":"No","author":[{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov"}]},{"intvolume":" 11","month":"06","scopus_import":"1","oa_version":"Published Version","abstract":[{"text":"The potential of immune-evasive mutation accumulation in the SARS-CoV-2 virus has led to its rapid spread, causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. The huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants has renewed interest in DNA vaccine technology. Here, we report the rapid generation and immunological evaluation of novel DNA vaccine candidates against the Wuhan-Hu-1 and Omicron variants based on the RBD protein fused with the Potato virus X coat protein (PVXCP). The delivery of DNA vaccines using electroporation in a two-dose regimen induced high-antibody titers and profound cellular responses in mice. The antibody titers induced against the Omicron variant of the vaccine were sufficient for effective protection against both Omicron and Wuhan-Hu-1 virus infections. The PVXCP protein in the vaccine construct shifted the immune response to the favorable Th1-like type and provided the oligomerization of RBD-PVXCP protein. Naked DNA delivery by needle-free injection allowed us to achieve antibody titers comparable with mRNA-LNP delivery in rabbits. These data identify the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study.","lang":"eng"}],"volume":11,"issue":"6","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"13244","checksum":"8f484c0f30f8699c589b1c29a0fd7d7f","success":1,"date_updated":"2023-07-18T07:25:43Z","file_size":2339746,"creator":"dernst","date_created":"2023-07-18T07:25:43Z","file_name":"2023_Vaccines_Dormeshkin.pdf"}],"publication_status":"published","publication_identifier":{"eissn":["2076-393X"]},"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","_id":"13232","file_date_updated":"2023-07-18T07:25:43Z","department":[{"_id":"LeSa"}],"ddc":["570"],"date_updated":"2023-08-02T06:31:19Z","oa":1,"publisher":"MDPI","quality_controlled":"1","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. The authors express their gratitude to the Institute of Physiology of the National Academy of Sciences of Belarus for providing assistance in keeping laboratory animals.","date_created":"2023-07-16T22:01:10Z","doi":"10.3390/vaccines11061014","date_published":"2023-06-01T00:00:00Z","publication":"Vaccines","day":"01","year":"2023","isi":1,"has_accepted_license":"1","article_number":"1014","title":"Design and immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein","article_processing_charge":"No","external_id":{"isi":["001017740000001"]},"author":[{"first_name":"Dmitri","last_name":"Dormeshkin","full_name":"Dormeshkin, Dmitri"},{"first_name":"Mikalai","last_name":"Katsin","full_name":"Katsin, Mikalai"},{"first_name":"Maria","full_name":"Stegantseva, Maria","last_name":"Stegantseva"},{"first_name":"Sergey","last_name":"Golenchenko","full_name":"Golenchenko, Sergey"},{"first_name":"Michail","full_name":"Shapira, Michail","last_name":"Shapira"},{"last_name":"Dubovik","full_name":"Dubovik, Simon","first_name":"Simon"},{"last_name":"Lutskovich","full_name":"Lutskovich, Dzmitry","first_name":"Dzmitry"},{"orcid":"0000-0003-2091-526X","full_name":"Kavaleuski, Anton","last_name":"Kavaleuski","first_name":"Anton","id":"62304f89-eb97-11eb-a6c2-8903dd183976"},{"full_name":"Meleshko, Alexander","last_name":"Meleshko","first_name":"Alexander"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"short":"D. Dormeshkin, M. Katsin, M. Stegantseva, S. Golenchenko, M. Shapira, S. Dubovik, D. Lutskovich, A. Kavaleuski, A. Meleshko, Vaccines 11 (2023).","ieee":"D. Dormeshkin et al., “Design and immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein,” Vaccines, vol. 11, no. 6. MDPI, 2023.","apa":"Dormeshkin, D., Katsin, M., Stegantseva, M., Golenchenko, S., Shapira, M., Dubovik, S., … Meleshko, A. (2023). Design and immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein. Vaccines. MDPI. https://doi.org/10.3390/vaccines11061014","ama":"Dormeshkin D, Katsin M, Stegantseva M, et al. Design and immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein. Vaccines. 2023;11(6). doi:10.3390/vaccines11061014","mla":"Dormeshkin, Dmitri, et al. “Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein.” Vaccines, vol. 11, no. 6, 1014, MDPI, 2023, doi:10.3390/vaccines11061014.","ista":"Dormeshkin D, Katsin M, Stegantseva M, Golenchenko S, Shapira M, Dubovik S, Lutskovich D, Kavaleuski A, Meleshko A. 2023. Design and immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein. Vaccines. 11(6), 1014.","chicago":"Dormeshkin, Dmitri, Mikalai Katsin, Maria Stegantseva, Sergey Golenchenko, Michail Shapira, Simon Dubovik, Dzmitry Lutskovich, Anton Kavaleuski, and Alexander Meleshko. “Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein.” Vaccines. MDPI, 2023. https://doi.org/10.3390/vaccines11061014."}},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ieee":"V. Kravchuk, “Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog,” Institute of Science and Technology Austria, 2023.","short":"V. Kravchuk, Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog, Institute of Science and Technology Austria, 2023.","apa":"Kravchuk, V. (2023). Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12781","ama":"Kravchuk V. Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. 2023. doi:10.15479/at:ista:12781","mla":"Kravchuk, Vladyslav. Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12781.","ista":"Kravchuk V. 2023. Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. Institute of Science and Technology Austria.","chicago":"Kravchuk, Vladyslav. “Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12781."},"title":"Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog","article_processing_charge":"No","author":[{"first_name":"Vladyslav","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","last_name":"Kravchuk","full_name":"Kravchuk, Vladyslav"}],"project":[{"_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E","grant_number":"25541","name":"Structural characterization of E. coli complex I: an important mechanistic model"},{"_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","call_identifier":"H2020","grant_number":"101020697","name":"Structure and mechanism of respiratory chain molecular machines"}],"day":"23","year":"2023","has_accepted_license":"1","date_created":"2023-03-31T12:24:42Z","doi":"10.15479/at:ista:12781","date_published":"2023-03-23T00:00:00Z","page":"127","publisher":"Institute of Science and Technology Austria","ddc":["570","572"],"date_updated":"2023-08-04T08:54:51Z","supervisor":[{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2023-04-20T07:02:59Z","department":[{"_id":"GradSch"},{"_id":"LeSa"}],"_id":"12781","status":"public","type":"dissertation","language":[{"iso":"eng"}],"file":[{"file_id":"12852","checksum":"5ebb6345cb4119f93460c81310265a6d","embargo":"2024-04-20","access_level":"closed","relation":"main_file","content_type":"application/pdf","embargo_to":"local","date_created":"2023-04-19T14:33:41Z","file_name":"VladyslavKravchuk_PhD_Thesis_PostSub_Final_1.pdf","creator":"vkravchu","date_updated":"2023-04-19T14:33:41Z","file_size":6071553},{"file_name":"VladyslavKravchuk_PhD_Thesis_PostSub_Final.docx","date_created":"2023-04-19T14:33:52Z","file_size":19468766,"date_updated":"2023-04-20T07:02:59Z","creator":"vkravchu","embargo":"2024-04-20","file_id":"12853","checksum":"c12055c48411d030d2afa51de2166221","embargo_to":"local","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"isbn":["978-3-99078-029-9"],"issn":["2663-337X"]},"ec_funded":1,"related_material":{"record":[{"relation":"part_of_dissertation","id":"12138","status":"public"}]},"oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"}],"abstract":[{"text":"Most energy in humans is produced in form of ATP by the mitochondrial respiratory chain consisting of several protein assemblies embedded into lipid membrane (complexes I-V). Complex I is the first and the largest enzyme of the respiratory chain which is essential for energy production. It couples the transfer of two electrons from NADH to ubiquinone with proton translocation across bacterial or inner mitochondrial membrane. The coupling mechanism between electron transfer and proton translocation is one of the biggest enigma in bioenergetics and structural biology. Even though the enzyme has been studied for decades, only recent technological advances in cryo-EM allowed its extensive structural investigation. \r\n\r\nComplex I from E.coli appears to be of special importance because it is a perfect model system with a rich mutant library, however the structure of the entire complex was unknown. In this thesis I have resolved structures of the minimal complex I version from E. coli in different states including reduced, inhibited, under reaction turnover and several others. Extensive structural analyses of these structures and comparison to structures from other species allowed to derive general features of conformational dynamics and propose a universal coupling mechanism. The mechanism is straightforward, robust and consistent with decades of experimental data available for complex I from different species. \r\n\r\nCyanobacterial NDH (cyanobacterial complex I) is a part of broad complex I superfamily and was studied as well in this thesis. It plays an important role in cyclic electron transfer (CET), during which electrons are cycled within PSI through ferredoxin and plastoquinone to generate proton gradient without NADPH production. Here, I solved structure of NDH and revealed additional state, which was not observed before. The novel “resting” state allowed to propose the mechanism of CET regulation. Moreover, conformational dynamics of NDH resembles one in complex I which suggest more broad universality of the proposed coupling mechanism.\r\n\r\nIn summary, results presented here helped to interpret decades of experimental data for complex I and contributed to fundamental mechanistic understanding of protein function.\r\n","lang":"eng"}],"month":"03","alternative_title":["ISTA Thesis"]},{"file_date_updated":"2023-08-14T07:01:12Z","department":[{"_id":"LeSa"}],"ddc":["570"],"date_updated":"2023-12-13T12:06:56Z","status":"public","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"14040","volume":14,"file":[{"checksum":"3b9043df3d51c300f9be95eac3ff9d0b","file_id":"14044","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2023-08-14T07:01:12Z","file_name":"2023_NatureComm_Zhao.pdf","creator":"dernst","date_updated":"2023-08-14T07:01:12Z","file_size":2315325}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2041-1723"]},"publication_status":"published","month":"08","intvolume":" 14","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Robust oxygenic photosynthesis requires a suite of accessory factors to ensure efficient assembly and repair of the oxygen-evolving photosystem two (PSII) complex. The highly conserved Ycf48 assembly factor binds to the newly synthesized D1 reaction center polypeptide and promotes the initial steps of PSII assembly, but its binding site is unclear. Here we use cryo-electron microscopy to determine the structure of a cyanobacterial PSII D1/D2 reaction center assembly complex with Ycf48 attached. Ycf48, a 7-bladed beta propeller, binds to the amino-acid residues of D1 that ultimately ligate the water-oxidising Mn4CaO5 cluster, thereby preventing the premature binding of Mn2+ and Ca2+ ions and protecting the site from damage. Interactions with D2 help explain how Ycf48 promotes assembly of the D1/D2 complex. Overall, our work provides valuable insights into the early stages of PSII assembly and the structural changes that create the binding site for the Mn4CaO5 cluster."}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"title":"The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis","author":[{"last_name":"Zhao","full_name":"Zhao, Ziyu","first_name":"Ziyu"},{"last_name":"Vercellino","orcid":"0000-0001-5618-3449","full_name":"Vercellino, Irene","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","first_name":"Irene"},{"full_name":"Knoppová, Jana","last_name":"Knoppová","first_name":"Jana"},{"first_name":"Roman","last_name":"Sobotka","full_name":"Sobotka, Roman"},{"first_name":"James W.","last_name":"Murray","full_name":"Murray, James W."},{"first_name":"Peter J.","full_name":"Nixon, Peter J.","last_name":"Nixon"},{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Josef","full_name":"Komenda, Josef","last_name":"Komenda"}],"article_processing_charge":"Yes","external_id":{"isi":["001042606700004"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"short":"Z. Zhao, I. Vercellino, J. Knoppová, R. Sobotka, J.W. Murray, P.J. Nixon, L.A. Sazanov, J. Komenda, Nature Communications 14 (2023).","ieee":"Z. Zhao et al., “The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis,” Nature Communications, vol. 14. Springer Nature, 2023.","ama":"Zhao Z, Vercellino I, Knoppová J, et al. The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis. Nature Communications. 2023;14. doi:10.1038/s41467-023-40388-6","apa":"Zhao, Z., Vercellino, I., Knoppová, J., Sobotka, R., Murray, J. W., Nixon, P. J., … Komenda, J. (2023). The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-40388-6","mla":"Zhao, Ziyu, et al. “The Ycf48 Accessory Factor Occupies the Site of the Oxygen-Evolving Manganese Cluster during Photosystem II Biogenesis.” Nature Communications, vol. 14, 4681, Springer Nature, 2023, doi:10.1038/s41467-023-40388-6.","ista":"Zhao Z, Vercellino I, Knoppová J, Sobotka R, Murray JW, Nixon PJ, Sazanov LA, Komenda J. 2023. The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis. Nature Communications. 14, 4681.","chicago":"Zhao, Ziyu, Irene Vercellino, Jana Knoppová, Roman Sobotka, James W. Murray, Peter J. Nixon, Leonid A Sazanov, and Josef Komenda. “The Ycf48 Accessory Factor Occupies the Site of the Oxygen-Evolving Manganese Cluster during Photosystem II Biogenesis.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-40388-6."},"article_number":"4681","date_published":"2023-08-04T00:00:00Z","doi":"10.1038/s41467-023-40388-6","date_created":"2023-08-13T22:01:13Z","day":"04","publication":"Nature Communications","has_accepted_license":"1","isi":1,"year":"2023","quality_controlled":"1","publisher":"Springer Nature","oa":1,"acknowledgement":"P.J.N. and J.W.M. are grateful for the support of the Biotechnology & Biological Sciences Research Council (awards BB/L003260/1 and BB/P00931X/1). J. Knoppová, R.S. and J. Komenda were supported by the Czech Science Foundation (project 19-29225X) and by ERC project Photoredesign (no. 854126) and L.A.S. 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."},{"oa_version":"None","pmid":1,"abstract":[{"text":"The mitochondrial oxidative phosphorylation system is central to cellular metabolism. It comprises five enzymatic complexes and two mobile electron carriers that work in a mitochondrial respiratory chain. By coupling the oxidation of reducing equivalents coming into mitochondria to the generation and subsequent dissipation of a proton gradient across the inner mitochondrial membrane, this electron transport chain drives the production of ATP, which is then used as a primary energy carrier in virtually all cellular processes. Minimal perturbations of the respiratory chain activity are linked to diseases; therefore, it is necessary to understand how these complexes are assembled and regulated and how they function. In this Review, we outline the latest assembly models for each individual complex, and we also highlight the recent discoveries indicating that the formation of larger assemblies, known as respiratory supercomplexes, originates from the association of the intermediates of individual complexes. We then discuss how recent cryo-electron microscopy structures have been key to answering open questions on the function of the electron transport chain in mitochondrial respiration and how supercomplexes and other factors, including metabolites, can regulate the activity of the single complexes. When relevant, we discuss how these mechanisms contribute to physiology and outline their deregulation in human diseases.","lang":"eng"}],"intvolume":" 23","month":"02","scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["1471-0072"],"eissn":["1471-0080"]},"volume":23,"_id":"10182","status":"public","type":"journal_article","article_type":"original","date_updated":"2023-08-02T06:55:42Z","department":[{"_id":"LeSa"}],"quality_controlled":"1","publisher":"Springer Nature","publication":"Nature Reviews Molecular Cell Biology","day":"01","year":"2022","isi":1,"date_created":"2021-10-24T22:01:35Z","doi":"10.1038/s41580-021-00415-0","date_published":"2022-02-01T00:00:00Z","page":"141–161","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Vercellino, Irene, and Leonid A Sazanov. “The Assembly, Regulation and Function of the Mitochondrial Respiratory Chain.” Nature Reviews Molecular Cell Biology. Springer Nature, 2022. https://doi.org/10.1038/s41580-021-00415-0.","ista":"Vercellino I, Sazanov LA. 2022. The assembly, regulation and function of the mitochondrial respiratory chain. Nature Reviews Molecular Cell Biology. 23, 141–161.","mla":"Vercellino, Irene, and Leonid A. Sazanov. “The Assembly, Regulation and Function of the Mitochondrial Respiratory Chain.” Nature Reviews Molecular Cell Biology, vol. 23, Springer Nature, 2022, pp. 141–161, doi:10.1038/s41580-021-00415-0.","apa":"Vercellino, I., & Sazanov, L. A. (2022). The assembly, regulation and function of the mitochondrial respiratory chain. Nature Reviews Molecular Cell Biology. Springer Nature. https://doi.org/10.1038/s41580-021-00415-0","ama":"Vercellino I, Sazanov LA. The assembly, regulation and function of the mitochondrial respiratory chain. Nature Reviews Molecular Cell Biology. 2022;23:141–161. doi:10.1038/s41580-021-00415-0","ieee":"I. Vercellino and L. A. Sazanov, “The assembly, regulation and function of the mitochondrial respiratory chain,” Nature Reviews Molecular Cell Biology, vol. 23. Springer Nature, pp. 141–161, 2022.","short":"I. Vercellino, L.A. Sazanov, Nature Reviews Molecular Cell Biology 23 (2022) 141–161."},"title":"The assembly, regulation and function of the mitochondrial respiratory chain","external_id":{"pmid":["34621061"],"isi":["000705697100001"]},"article_processing_charge":"No","author":[{"orcid":" 0000-0001-5618-3449","full_name":"Vercellino, Irene","last_name":"Vercellino","first_name":"Irene","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}]},{"scopus_import":"1","intvolume":" 74","month":"06","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."}],"oa_version":"Published Version","pmid":1,"volume":74,"publication_status":"published","publication_identifier":{"issn":["0959-440X"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"11725","checksum":"72bdde48853643a32d42b75f54965c44","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2022_CurrentOpStructBiology_Kampjut.pdf","date_created":"2022-08-05T05:56:03Z","file_size":815607,"date_updated":"2022-08-05T05:56:03Z","creator":"dernst"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","keyword":["Molecular Biology","Structural Biology"],"status":"public","_id":"11167","department":[{"_id":"LeSa"}],"file_date_updated":"2022-08-05T05:56:03Z","date_updated":"2023-08-03T06:31:06Z","ddc":["570"],"oa":1,"quality_controlled":"1","publisher":"Elsevier","date_created":"2022-04-15T09:32:35Z","doi":"10.1016/j.sbi.2022.102350","date_published":"2022-06-01T00:00:00Z","year":"2022","isi":1,"has_accepted_license":"1","publication":"Current Opinion in Structural Biology","day":"01","article_number":"102350","external_id":{"isi":["000829029500020"],"pmid":["35316665"]},"article_processing_charge":"Yes (via OA deal)","author":[{"last_name":"Kampjut","full_name":"Kampjut, Domen","first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"title":"Structure of respiratory complex I – An emerging blueprint for the mechanism","citation":{"ista":"Kampjut D, Sazanov LA. 2022. Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. 74, 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.","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","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","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"file_date_updated":"2022-07-13T07:44:58Z","department":[{"_id":"LeSa"}],"ddc":["570"],"date_updated":"2023-08-03T11:51:58Z","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"11551","issue":"1","volume":5,"file":[{"success":1,"file_id":"11571","checksum":"965f88bbcef3fd0c3e121340555c4467","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_communicationsbiology_Molina-Granada.pdf","date_created":"2022-07-13T07:44:58Z","creator":"kschuh","file_size":2335369,"date_updated":"2022-07-13T07:44:58Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["23993642"]},"publication_status":"published","month":"06","intvolume":" 5","scopus_import":"1","pmid":1,"oa_version":"Published Version","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"}],"title":"Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit","author":[{"first_name":"David","last_name":"Molina-Granada","full_name":"Molina-Granada, David"},{"last_name":"González-Vioque","full_name":"González-Vioque, Emiliano","first_name":"Emiliano"},{"full_name":"Dibley, Marris G.","last_name":"Dibley","first_name":"Marris G."},{"last_name":"Cabrera-Pérez","full_name":"Cabrera-Pérez, Raquel","first_name":"Raquel"},{"first_name":"Antoni","last_name":"Vallbona-Garcia","full_name":"Vallbona-Garcia, Antoni"},{"first_name":"Javier","full_name":"Torres-Torronteras, Javier","last_name":"Torres-Torronteras"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"},{"first_name":"Michael T.","full_name":"Ryan, Michael T.","last_name":"Ryan"},{"last_name":"Cámara","full_name":"Cámara, Yolanda","first_name":"Yolanda"},{"first_name":"Ramon","last_name":"Martí","full_name":"Martí, Ramon"}],"article_processing_charge":"No","external_id":{"isi":["000815098500002"],"pmid":[" 35739187"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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).","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","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","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.","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.","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."},"article_number":"620","date_published":"2022-06-23T00:00:00Z","doi":"10.1038/s42003-022-03568-6","date_created":"2022-07-10T22:01:52Z","day":"23","publication":"Communications Biology","isi":1,"has_accepted_license":"1","year":"2022","quality_controlled":"1","publisher":"Springer Nature","oa":1,"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"},{"citation":{"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.","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.","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.","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.","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.","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","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"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000837950900001"],"pmid":["35861182"]},"article_processing_charge":"No","author":[{"full_name":"Gerle, Christoph","last_name":"Gerle","first_name":"Christoph"},{"first_name":"Jun-ichi","full_name":"Kishikawa, Jun-ichi","last_name":"Kishikawa"},{"full_name":"Yamaguchi, Tomoko","last_name":"Yamaguchi","first_name":"Tomoko"},{"first_name":"Atsuko","last_name":"Nakanishi","full_name":"Nakanishi, Atsuko"},{"first_name":"Mehmet Orkun","id":"d25163e5-8d53-11eb-a251-e6dd8ea1b8ef","orcid":"0000-0002-3219-2022","full_name":"Çoruh, Mehmet Orkun","last_name":"Çoruh"},{"first_name":"Fumiaki","full_name":"Makino, Fumiaki","last_name":"Makino"},{"last_name":"Miyata","full_name":"Miyata, Tomoko","first_name":"Tomoko"},{"first_name":"Akihiro","full_name":"Kawamoto, Akihiro","last_name":"Kawamoto"},{"first_name":"Ken","last_name":"Yokoyama","full_name":"Yokoyama, Ken"},{"first_name":"Keiichi","full_name":"Namba, Keiichi","last_name":"Namba"},{"first_name":"Genji","last_name":"Kurisu","full_name":"Kurisu, Genji"},{"full_name":"Kato, Takayuki","last_name":"Kato","first_name":"Takayuki"}],"title":"Structures of multisubunit membrane complexes with the CRYO ARM 200","year":"2022","isi":1,"has_accepted_license":"1","publication":"Microscopy","day":"01","page":"249-261","date_created":"2022-07-25T10:04:58Z","doi":"10.1093/jmicro/dfac037","date_published":"2022-10-01T00:00:00Z","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.","oa":1,"quality_controlled":"1","publisher":"Oxford University Press","date_updated":"2023-08-03T12:13:37Z","ddc":["570"],"file_date_updated":"2023-02-03T08:34:48Z","department":[{"_id":"LeSa"}],"_id":"11648","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","keyword":["Radiology","Nuclear Medicine and imaging","Instrumentation","Structural Biology"],"status":"public","publication_status":"published","publication_identifier":{"eissn":["2050-5701"],"issn":["2050-5698"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"12498","checksum":"23b51c163636bf9313f7f0818312e67e","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_Microscopy_Gerle.pdf","date_created":"2023-02-03T08:34:48Z","creator":"dernst","file_size":7812696,"date_updated":"2023-02-03T08:34:48Z"}],"volume":71,"issue":"5","abstract":[{"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.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","intvolume":" 71","month":"10"},{"citation":{"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.","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.","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.","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.","short":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, L.A. Sazanov, Nature 609 (2022) 808–814.","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","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"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Kravchuk, Vladyslav","last_name":"Kravchuk","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","first_name":"Vladyslav"},{"id":"5D8C9660-5D49-11EA-8188-567B3DDC885E","first_name":"Olga","last_name":"Petrova","full_name":"Petrova, Olga"},{"id":"37233050-F248-11E8-B48F-1D18A9856A87","first_name":"Domen","full_name":"Kampjut, Domen","last_name":"Kampjut"},{"last_name":"Wojciechowska-Bason","full_name":"Wojciechowska-Bason, Anna","first_name":"Anna"},{"first_name":"Zara","full_name":"Breese, Zara","last_name":"Breese"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","external_id":{"isi":["000854788200001"],"pmid":["36104567"]},"title":"A universal coupling mechanism of respiratory complex I","project":[{"name":"Structural characterization of E. coli complex I: an important mechanistic model","grant_number":"25541","_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"101020697","name":"Structure and mechanism of respiratory chain molecular machines","call_identifier":"H2020","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3"}],"isi":1,"has_accepted_license":"1","year":"2022","day":"22","publication":"Nature","page":"808-814","doi":"10.1038/s41586-022-05199-7","date_published":"2022-09-22T00:00:00Z","date_created":"2023-01-12T12:04:33Z","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).","publisher":"Springer Nature","quality_controlled":"1","oa":1,"date_updated":"2023-08-04T08:54:52Z","ddc":["572"],"department":[{"_id":"LeSa"}],"file_date_updated":"2023-05-30T17:07:05Z","_id":"12138","type":"journal_article","article_type":"original","status":"public","keyword":["Multidisciplinary"],"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"publication_status":"published","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"d42a93e24f59e883ef0b5429832391d0","file_id":"13104","file_size":1425655,"date_updated":"2023-05-30T17:05:31Z","creator":"lsazanov","file_name":"EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf","date_created":"2023-05-30T17:05:31Z"},{"file_name":"EcCxI_manuscript_rev3_SI_All_opt_upd.pdf","date_created":"2023-05-30T17:07:05Z","file_size":9842513,"date_updated":"2023-05-30T17:07:05Z","creator":"lsazanov","success":1,"checksum":"5422bc0a73b3daadafa262c7ea6deae3","file_id":"13105","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"volume":609,"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41586-022-05457-8"},{"url":"https://ista.ac.at/en/news/proton-dominos-kick-off-life/","relation":"press_release","description":"News on ISTA website"}],"record":[{"relation":"dissertation_contains","id":"12781","status":"public"}]},"issue":"7928","ec_funded":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"abstract":[{"lang":"eng","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."}],"pmid":1,"oa_version":"Submitted Version","scopus_import":"1","month":"09","intvolume":" 609"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","keyword":["Immunology","Immunology and Allergy","COVID-19","SARS-CoV-2","synthetic library","RBD","neutralization nanobody","VHH"],"status":"public","_id":"12252","file_date_updated":"2023-01-30T09:22:26Z","department":[{"_id":"LeSa"}],"date_updated":"2023-08-04T09:49:24Z","ddc":["570"],"scopus_import":"1","intvolume":" 13","month":"09","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","volume":13,"publication_status":"published","publication_identifier":{"issn":["1664-3224"]},"language":[{"iso":"eng"}],"file":[{"file_name":"2022_FrontiersImmunology_Dormeshkin.pdf","date_created":"2023-01-30T09:22:26Z","file_size":5695892,"date_updated":"2023-01-30T09:22:26Z","creator":"dernst","success":1,"file_id":"12443","checksum":"f8f5d8110710033d0532e7e08bf9dad4","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"article_number":"965446","article_processing_charge":"No","external_id":{"isi":["000862479100001"]},"author":[{"last_name":"Dormeshkin","full_name":"Dormeshkin, Dmitri","first_name":"Dmitri"},{"first_name":"Michail","last_name":"Shapira","full_name":"Shapira, Michail"},{"first_name":"Simon","full_name":"Dubovik, Simon","last_name":"Dubovik"},{"first_name":"Anton","id":"4968f7ad-eb97-11eb-a6c2-8ed382e8912c","full_name":"Kavaleuski, Anton","orcid":"0000-0003-2091-526X","last_name":"Kavaleuski"},{"full_name":"Katsin, Mikalai","last_name":"Katsin","first_name":"Mikalai"},{"first_name":"Alexandr","full_name":"Migas, Alexandr","last_name":"Migas"},{"last_name":"Meleshko","full_name":"Meleshko, Alexander","first_name":"Alexander"},{"first_name":"Sergei","full_name":"Semyonov, Sergei","last_name":"Semyonov"}],"title":"Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library","citation":{"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.","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.","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","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"quality_controlled":"1","publisher":"Frontiers Media","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.","date_created":"2023-01-16T09:56:57Z","date_published":"2022-09-16T00:00:00Z","doi":"10.3389/fimmu.2022.965446","year":"2022","has_accepted_license":"1","isi":1,"publication":"Frontiers in Immunology","day":"16"}]