[{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial and ‘de Luxe’ Mammalian Versions.” In Mechanisms of Primary Energy Transduction in Biology , edited by Mårten Wikström, 25–59. Mechanisms of Primary Energy Transduction in Biology . Royal Society of Chemistry, 2017. https://doi.org/10.1039/9781788010405-00025.","ista":"Sazanov LA. 2017.Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In: Mechanisms of primary energy transduction in biology . , 25–59.","mla":"Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial and ‘de Luxe’ Mammalian Versions.” Mechanisms of Primary Energy Transduction in Biology , edited by Mårten Wikström, Royal Society of Chemistry, 2017, pp. 25–59, doi:10.1039/9781788010405-00025.","apa":"Sazanov, L. A. (2017). Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In M. Wikström (Ed.), Mechanisms of primary energy transduction in biology (pp. 25–59). Royal Society of Chemistry. https://doi.org/10.1039/9781788010405-00025","ama":"Sazanov LA. Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In: Wikström M, ed. Mechanisms of Primary Energy Transduction in Biology . Mechanisms of Primary Energy Transduction in Biology . Royal Society of Chemistry; 2017:25-59. doi:10.1039/9781788010405-00025","ieee":"L. A. Sazanov, “Structure of respiratory complex I: ‘Minimal’ bacterial and ‘de luxe’ mammalian versions,” in Mechanisms of primary energy transduction in biology , M. Wikström, Ed. Royal Society of Chemistry, 2017, pp. 25–59.","short":"L.A. Sazanov, in:, M. Wikström (Ed.), Mechanisms of Primary Energy Transduction in Biology , Royal Society of Chemistry, 2017, pp. 25–59."},"date_updated":"2021-01-12T07:56:59Z","editor":[{"full_name":"Wikström, Mårten","last_name":"Wikström","first_name":"Mårten"}],"department":[{"_id":"LeSa"}],"title":"Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions","publist_id":"7379","author":[{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"_id":"444","series_title":"Mechanisms of Primary Energy Transduction in Biology ","status":"public","type":"book_chapter","day":"29","publication":"Mechanisms of primary energy transduction in biology ","language":[{"iso":"eng"}],"publication_identifier":{"isbn":["978-1-78262-865-1"]},"publication_status":"published","year":"2017","date_published":"2017-11-29T00:00:00Z","doi":"10.1039/9781788010405-00025","date_created":"2018-12-11T11:46:30Z","page":"25 - 59","oa_version":"None","abstract":[{"lang":"eng","text":"Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy generation, contributing to the proton motive force used to produce ATP. It couples the transfer of two electrons between NADH and quinone to translocation of four protons across the membrane. It is the largest protein assembly of bacterial and mitochondrial respiratory chains, composed, in mammals, of up to 45 subunits with a total molecular weight of ∼1 MDa. Bacterial enzyme is about half the size, providing the important “minimal” model of complex I. The l-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. Previously, we have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus and of the membrane domain from Escherichia coli, followed by the atomic structure of intact, entire complex I from T. thermophilus. Recently, we have solved by cryo-EM a first complete atomic structure of mammalian (ovine) mitochondrial complex I. Core subunits are well conserved from the bacterial version, whilst supernumerary subunits form an interlinked, stabilizing shell around the core. Subunits containing additional cofactors, including Zn ion, NADPH and phosphopantetheine, probably have regulatory roles. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The structure of mammalian enzyme provides many insights into complex I mechanism, assembly, maturation and dysfunction, allowing detailed molecular analysis of disease-causing mutations."}],"month":"11","quality_controlled":"1","publisher":"Royal Society of Chemistry"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Letts, James A, and Leonid A Sazanov. “Clarifying the Supercomplex: The Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature Structural and Molecular Biology. Nature Publishing Group, 2017. https://doi.org/10.1038/nsmb.3460.","ista":"Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. 24(10), 800–808.","mla":"Letts, James A., and Leonid A. Sazanov. “Clarifying the Supercomplex: The Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature Structural and Molecular Biology, vol. 24, no. 10, Nature Publishing Group, 2017, pp. 800–08, doi:10.1038/nsmb.3460.","ieee":"J. A. Letts and L. A. Sazanov, “Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain,” Nature Structural and Molecular Biology, vol. 24, no. 10. Nature Publishing Group, pp. 800–808, 2017.","short":"J.A. Letts, L.A. Sazanov, Nature Structural and Molecular Biology 24 (2017) 800–808.","ama":"Letts JA, Sazanov LA. Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. 2017;24(10):800-808. doi:10.1038/nsmb.3460","apa":"Letts, J. A., & Sazanov, L. A. (2017). Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. Nature Publishing Group. https://doi.org/10.1038/nsmb.3460"},"title":"Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain","author":[{"first_name":"James A","id":"322DA418-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9864-3586","full_name":"Letts, James A","last_name":"Letts"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"7304","project":[{"grant_number":"701309","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)","call_identifier":"H2020","_id":"2590DB08-B435-11E9-9278-68D0E5697425"}],"day":"05","publication":"Nature Structural and Molecular Biology","has_accepted_license":"1","year":"2017","date_published":"2017-10-05T00:00:00Z","doi":"10.1038/nsmb.3460","date_created":"2018-12-11T11:46:54Z","page":"800 - 808","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"ddc":["572"],"date_updated":"2021-01-12T08:01:17Z","file_date_updated":"2020-07-14T12:46:36Z","department":[{"_id":"LeSa"}],"_id":"515","status":"public","type":"journal_article","article_type":"original","file":[{"checksum":"9bc7e8c41b43636dd7566289e511f096","file_id":"6993","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2019-11-07T12:51:07Z","file_name":"29893_2_merged_1501257589_red.pdf","date_updated":"2020-07-14T12:46:36Z","file_size":4118385,"creator":"lsazanov"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["15459993"]},"publication_status":"published","issue":"10","volume":24,"ec_funded":1,"oa_version":"Submitted Version","abstract":[{"lang":"eng","text":"The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome), as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the assembly and function of the SCs. Here we review and compare these recent studies and discuss how they have advanced our understanding of mitochondrial electron transport."}],"month":"10","intvolume":" 24","scopus_import":1},{"_id":"1186","status":"public","pubrep_id":"735","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)"},"ddc":["576","610"],"date_updated":"2021-01-12T06:48:56Z","department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:44:37Z","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus."}],"month":"12","intvolume":" 6","scopus_import":1,"file":[{"file_id":"4804","checksum":"e007d78b483bc59bf5ab98e9d42a6ec1","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IST-2017-735-v1+1_srep38094.pdf","date_created":"2018-12-12T10:10:18Z","creator":"system","file_size":2716045,"date_updated":"2020-07-14T12:44:37Z"}],"language":[{"iso":"eng"}],"publication_status":"published","volume":6,"article_number":"38094","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"short":"J. Gutierrez-Fernandez, M. Saleh, M. Alcorlo, A. Gómez Mejóa, D. Pantoja Uceda, M. Treviño, F. Vob, M. Abdullah, S. Galán Bartual, J. Seinen, P. Sánchez Murcia, F. Gago, M. Bruix, S. Hammerschmidt, J. Hermoso, Scientific Reports 6 (2016).","ieee":"J. Gutierrez-Fernandez et al., “Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.","apa":"Gutierrez-Fernandez, J., Saleh, M., Alcorlo, M., Gómez Mejóa, A., Pantoja Uceda, D., Treviño, M., … Hermoso, J. (2016). Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep38094","ama":"Gutierrez-Fernandez J, Saleh M, Alcorlo M, et al. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 2016;6. doi:10.1038/srep38094","mla":"Gutierrez-Fernandez, Javier, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports, vol. 6, 38094, Nature Publishing Group, 2016, doi:10.1038/srep38094.","ista":"Gutierrez-Fernandez J, Saleh M, Alcorlo M, Gómez Mejóa A, Pantoja Uceda D, Treviño M, Vob F, Abdullah M, Galán Bartual S, Seinen J, Sánchez Murcia P, Gago F, Bruix M, Hammerschmidt S, Hermoso J. 2016. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 6, 38094.","chicago":"Gutierrez-Fernandez, Javier, Malek Saleh, Martín Alcorlo, Alejandro Gómez Mejóa, David Pantoja Uceda, Miguel Treviño, Franziska Vob, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep38094."},"title":"Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis","author":[{"first_name":"Javier","id":"3D9511BA-F248-11E8-B48F-1D18A9856A87","last_name":"Gutierrez-Fernandez","full_name":"Gutierrez-Fernandez, Javier"},{"first_name":"Malek","full_name":"Saleh, Malek","last_name":"Saleh"},{"first_name":"Martín","full_name":"Alcorlo, Martín","last_name":"Alcorlo"},{"full_name":"Gómez Mejóa, Alejandro","last_name":"Gómez Mejóa","first_name":"Alejandro"},{"last_name":"Pantoja Uceda","full_name":"Pantoja Uceda, David","first_name":"David"},{"last_name":"Treviño","full_name":"Treviño, Miguel","first_name":"Miguel"},{"full_name":"Vob, Franziska","last_name":"Vob","first_name":"Franziska"},{"last_name":"Abdullah","full_name":"Abdullah, Mohammed","first_name":"Mohammed"},{"first_name":"Sergio","last_name":"Galán Bartual","full_name":"Galán Bartual, Sergio"},{"last_name":"Seinen","full_name":"Seinen, Jolien","first_name":"Jolien"},{"first_name":"Pedro","full_name":"Sánchez Murcia, Pedro","last_name":"Sánchez Murcia"},{"first_name":"Federico","full_name":"Gago, Federico","last_name":"Gago"},{"full_name":"Bruix, Marta","last_name":"Bruix","first_name":"Marta"},{"first_name":"Sven","last_name":"Hammerschmidt","full_name":"Hammerschmidt, Sven"},{"first_name":"Juan","last_name":"Hermoso","full_name":"Hermoso, Juan"}],"publist_id":"6167","acknowledgement":"We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD-2457 (Community of Madrid to JAH and FG).","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"day":"05","publication":"Scientific Reports","has_accepted_license":"1","year":"2016","date_published":"2016-12-05T00:00:00Z","doi":"10.1038/srep38094","date_created":"2018-12-11T11:50:36Z"},{"language":[{"iso":"eng"}],"publication_status":"published","ec_funded":1,"issue":"47","volume":291,"oa_version":"Submitted Version","abstract":[{"text":"NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. ","lang":"eng"}],"intvolume":" 291","month":"11","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114416/"}],"scopus_import":1,"date_updated":"2021-01-12T06:49:06Z","department":[{"_id":"LeSa"}],"_id":"1209","status":"public","type":"journal_article","publication":"Journal of Biological Chemistry","day":"18","year":"2016","date_created":"2018-12-11T11:50:44Z","date_published":"2016-11-18T00:00:00Z","doi":"10.1074/jbc.M116.735142","page":"24657 - 24675","acknowledgement":"J.A.S supported in part by a Medical Research D.G.Council UK Ph.D. fellowship.\r\nThis work was supported in part by European Union's 2020 Research and Innovation Program under Grant 701309. \r\n","oa":1,"publisher":"American Society for Biochemistry and Molecular Biology","quality_controlled":"1","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Letts, James A., et al. “Purification of Ovine Respiratory Complex i Results in a Highly Active and Stable Preparation.” Journal of Biological Chemistry, vol. 291, no. 47, American Society for Biochemistry and Molecular Biology, 2016, pp. 24657–75, doi:10.1074/jbc.M116.735142.","ama":"Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. 2016;291(47):24657-24675. doi:10.1074/jbc.M116.735142","apa":"Letts, J. A., Degliesposti, G., Fiedorczuk, K., Skehel, M., & Sazanov, L. A. (2016). Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M116.735142","ieee":"J. A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, and L. A. Sazanov, “Purification of ovine respiratory complex i results in a highly active and stable preparation,” Journal of Biological Chemistry, vol. 291, no. 47. American Society for Biochemistry and Molecular Biology, pp. 24657–24675, 2016.","short":"J.A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, L.A. Sazanov, Journal of Biological Chemistry 291 (2016) 24657–24675.","chicago":"Letts, James A, Gianluca Degliesposti, Karol Fiedorczuk, Mark Skehel, and Leonid A Sazanov. “Purification of Ovine Respiratory Complex i Results in a Highly Active and Stable Preparation.” Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology, 2016. https://doi.org/10.1074/jbc.M116.735142.","ista":"Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. 2016. Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. 291(47), 24657–24675."},"title":"Purification of ovine respiratory complex i results in a highly active and stable preparation","author":[{"id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"James A","full_name":"Letts, James A","orcid":"0000-0002-9864-3586","last_name":"Letts"},{"first_name":"Gianluca","last_name":"Degliesposti","full_name":"Degliesposti, Gianluca"},{"first_name":"Karol","id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","full_name":"Fiedorczuk, Karol","last_name":"Fiedorczuk"},{"full_name":"Skehel, Mark","last_name":"Skehel","first_name":"Mark"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"publist_id":"6139","project":[{"name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)","_id":"2593EBD6-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"2590DB08-B435-11E9-9278-68D0E5697425","grant_number":"701309","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)"}]},{"abstract":[{"lang":"eng","text":"Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations."}],"pmid":1,"oa_version":"Submitted Version","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164932/","open_access":"1"}],"scopus_import":1,"intvolume":" 538","month":"10","publication_status":"published","language":[{"iso":"eng"}],"ec_funded":1,"volume":538,"issue":"7625","_id":"1226","article_type":"original","type":"journal_article","status":"public","date_updated":"2021-01-12T06:49:13Z","department":[{"_id":"LeSa"}],"oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","year":"2016","publication":"Nature","day":"20","page":"406 - 410","date_created":"2018-12-11T11:50:49Z","date_published":"2016-10-20T00:00:00Z","doi":"10.1038/nature19794","project":[{"name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)","_id":"2593EBD6-B435-11E9-9278-68D0E5697425"},{"_id":"2590DB08-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)","grant_number":"701309"}],"citation":{"ieee":"K. Fiedorczuk, J. A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, and L. A. Sazanov, “Atomic structure of the entire mammalian mitochondrial complex i,” Nature, vol. 538, no. 7625. Nature Publishing Group, pp. 406–410, 2016.","short":"K. Fiedorczuk, J.A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, L.A. Sazanov, Nature 538 (2016) 406–410.","apa":"Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., & Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19794","ama":"Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 2016;538(7625):406-410. doi:10.1038/nature19794","mla":"Fiedorczuk, Karol, et al. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature, vol. 538, no. 7625, Nature Publishing Group, 2016, pp. 406–10, doi:10.1038/nature19794.","ista":"Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. 2016. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 538(7625), 406–410.","chicago":"Fiedorczuk, Karol, James A Letts, Gianluca Degliesposti, Karol Kaszuba, Mark Skehel, and Leonid A Sazanov. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19794."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","external_id":{"pmid":["27595392"]},"author":[{"id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","first_name":"Karol","last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol"},{"first_name":"James A","id":"322DA418-F248-11E8-B48F-1D18A9856A87","last_name":"Letts","full_name":"Letts, James A","orcid":"0000-0002-9864-3586"},{"first_name":"Gianluca","full_name":"Degliesposti, Gianluca","last_name":"Degliesposti"},{"full_name":"Kaszuba, Karol","last_name":"Kaszuba","id":"3FDF9472-F248-11E8-B48F-1D18A9856A87","first_name":"Karol"},{"last_name":"Skehel","full_name":"Skehel, Mark","first_name":"Mark"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov"}],"publist_id":"6108","title":"Atomic structure of the entire mammalian mitochondrial complex i"},{"_id":"1232","project":[{"name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)","_id":"2593EBD6-B435-11E9-9278-68D0E5697425"}],"status":"public","type":"journal_article","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Letts JA, Fiedorczuk K, Sazanov LA. 2016. The architecture of respiratory supercomplexes. Nature. 537(7622), 644–648.","chicago":"Letts, James A, Karol Fiedorczuk, and Leonid A Sazanov. “The Architecture of Respiratory Supercomplexes.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19774.","apa":"Letts, J. A., Fiedorczuk, K., & Sazanov, L. A. (2016). The architecture of respiratory supercomplexes. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19774","ama":"Letts JA, Fiedorczuk K, Sazanov LA. The architecture of respiratory supercomplexes. Nature. 2016;537(7622):644-648. doi:10.1038/nature19774","short":"J.A. Letts, K. Fiedorczuk, L.A. Sazanov, Nature 537 (2016) 644–648.","ieee":"J. A. Letts, K. Fiedorczuk, and L. A. Sazanov, “The architecture of respiratory supercomplexes,” Nature, vol. 537, no. 7622. Nature Publishing Group, pp. 644–648, 2016.","mla":"Letts, James A., et al. “The Architecture of Respiratory Supercomplexes.” Nature, vol. 537, no. 7622, Nature Publishing Group, 2016, pp. 644–48, doi:10.1038/nature19774."},"date_updated":"2021-01-12T06:49:16Z","department":[{"_id":"LeSa"}],"title":"The architecture of respiratory supercomplexes","publist_id":"6102","author":[{"full_name":"Letts, James A","orcid":"0000-0002-9864-3586","last_name":"Letts","id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"James A"},{"id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","first_name":"Karol","last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"acknowledgement":"We thank the MRC LMB Cambridge for the use of the Titan Krios microscope. Data processing was performed using the IST high-performance computer cluster. J.A.L. holds a long-term fellowship from FEBS. K.F. is partially funded by a MRC UK PhD fellowship.","oa_version":"None","abstract":[{"lang":"eng","text":"Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII 2 CIV (the respirasome) - a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.8 Å and 6.7 Å, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII 2 at 7.8 Å resolution. All observed density can be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain."}],"intvolume":" 537","month":"09","quality_controlled":"1","publisher":"Nature Publishing Group","scopus_import":1,"publication":"Nature","language":[{"iso":"eng"}],"day":"29","year":"2016","publication_status":"published","date_created":"2018-12-11T11:50:51Z","doi":"10.1038/nature19774","issue":"7622","volume":537,"date_published":"2016-09-29T00:00:00Z","page":"644 - 648"},{"_id":"1276","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)"},"status":"public","pubrep_id":"691","date_updated":"2021-01-12T06:49:34Z","ddc":["576"],"department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:44:42Z","abstract":[{"lang":"eng","text":"The cytochrome (cyt) bc 1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q i-site to facilitate binding of half-protonated semiquinone-a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q i-site."}],"oa_version":"Published Version","scopus_import":1,"month":"09","intvolume":" 6","publication_status":"published","file":[{"file_id":"5261","checksum":"07c591c1250ebef266333cbc3228b4dd","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:17:09Z","file_name":"IST-2016-691-v1+1_srep33607.pdf","date_updated":"2020-07-14T12:44:42Z","file_size":1960563,"creator":"system"}],"language":[{"iso":"eng"}],"volume":6,"article_number":"33607","citation":{"chicago":"Postila, Pekka, Karol Kaszuba, Patryk Kuleta, Ilpo Vattulainen, Marcin Sarewicz, Artur Osyczka, and Tomasz Róg. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep33607.","ista":"Postila P, Kaszuba K, Kuleta P, Vattulainen I, Sarewicz M, Osyczka A, Róg T. 2016. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 6, 33607.","mla":"Postila, Pekka, et al. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports, vol. 6, 33607, Nature Publishing Group, 2016, doi:10.1038/srep33607.","ieee":"P. Postila et al., “Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.","short":"P. Postila, K. Kaszuba, P. Kuleta, I. Vattulainen, M. Sarewicz, A. Osyczka, T. Róg, Scientific Reports 6 (2016).","apa":"Postila, P., Kaszuba, K., Kuleta, P., Vattulainen, I., Sarewicz, M., Osyczka, A., & Róg, T. (2016). Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep33607","ama":"Postila P, Kaszuba K, Kuleta P, et al. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 2016;6. doi:10.1038/srep33607"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publist_id":"6040","author":[{"first_name":"Pekka","last_name":"Postila","full_name":"Postila, Pekka"},{"first_name":"Karol","id":"3FDF9472-F248-11E8-B48F-1D18A9856A87","last_name":"Kaszuba","full_name":"Kaszuba, Karol"},{"first_name":"Patryk","full_name":"Kuleta, Patryk","last_name":"Kuleta"},{"last_name":"Vattulainen","full_name":"Vattulainen, Ilpo","first_name":"Ilpo"},{"last_name":"Sarewicz","full_name":"Sarewicz, Marcin","first_name":"Marcin"},{"first_name":"Artur","full_name":"Osyczka, Artur","last_name":"Osyczka"},{"first_name":"Tomasz","full_name":"Róg, Tomasz","last_name":"Róg"}],"title":"Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex","acknowledgement":"We wish to thank CSC – IT Centre for Science (Espoo, Finland) for computational resources. For financial support, we wish to thank the Academy of Finland (TR, IV and PAP; Center of Excellence in Biomembrane Research (IV, TR)), the Finnish Doctoral Programme in Computational Sciences (KK), the Sigrid Juselius Foundation (IV), the Paulo Foundation (PAP), and the European Research Council (IV, TR; Advanced Grant project CROWDED-PRO-LIPIDS). AO acknowledges The Wellcome Trust International Senior Research Fellowship.","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"has_accepted_license":"1","year":"2016","day":"26","publication":"Scientific Reports","date_published":"2016-09-26T00:00:00Z","doi":"10.1038/srep33607","date_created":"2018-12-11T11:51:05Z"},{"acknowledgement":"This work was funded by the UK Medical Research Council.","oa_version":"None","abstract":[{"text":"Respiratory complex I transfers electrons from NADH to quinone, utilizing the reaction energy to translocate protons across the membrane. It is a key enzyme of the respiratory chain of many prokaryotic and most eukaryotic organisms. The reversible NADH oxidation reaction is facilitated in complex I by non-covalently bound flavin mononucleotide (FMN). Here we report that the catalytic activity of E. coli complex I with artificial electron acceptors potassium ferricyanide (FeCy) and hexaamineruthenium (HAR) is significantly inhibited in the enzyme pre-reduced by NADH. Further, we demonstrate that the inhibition is caused by reversible dissociation of FMN. The binding constant (Kd) for FMN increases from the femto- or picomolar range in oxidized complex I to the nanomolar range in the NADH reduced enzyme, with an FMN dissociation time constant of ~ 5 s. The oxidation state of complex I, rather than that of FMN, proved critical to the dissociation. Such dissociation is not observed with the T. thermophilus enzyme and our analysis suggests that the difference may be due to the unusually high redox potential of Fe-S cluster N1a in E. coli. It is possible that the enzyme attenuates ROS production in vivo by releasing FMN under highly reducing conditions.","lang":"eng"}],"intvolume":" 1857","month":"11","scopus_import":1,"quality_controlled":"1","publisher":"Elsevier","publication":"Biochimica et Biophysica Acta - Bioenergetics","language":[{"iso":"eng"}],"day":"01","publication_status":"published","year":"2016","date_created":"2018-12-11T11:51:09Z","issue":"11","doi":"10.1016/j.bbabio.2016.08.008","volume":1857,"date_published":"2016-11-01T00:00:00Z","page":"1777 - 1785","_id":"1288","status":"public","type":"journal_article","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:49:38Z","citation":{"ista":"Holt P, Efremov R, Nakamaru Ogiso E, Sazanov LA. 2016. Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 1857(11), 1777–1785.","chicago":"Holt, Peter, Rouslan Efremov, Eiko Nakamaru Ogiso, and Leonid A Sazanov. “Reversible FMN Dissociation from Escherichia Coli Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics. Elsevier, 2016. https://doi.org/10.1016/j.bbabio.2016.08.008.","apa":"Holt, P., Efremov, R., Nakamaru Ogiso, E., & Sazanov, L. A. (2016). Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. Elsevier. https://doi.org/10.1016/j.bbabio.2016.08.008","ama":"Holt P, Efremov R, Nakamaru Ogiso E, Sazanov LA. Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 2016;1857(11):1777-1785. doi:10.1016/j.bbabio.2016.08.008","ieee":"P. Holt, R. Efremov, E. Nakamaru Ogiso, and L. A. Sazanov, “Reversible FMN dissociation from Escherichia coli respiratory complex I,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 11. Elsevier, pp. 1777–1785, 2016.","short":"P. Holt, R. Efremov, E. Nakamaru Ogiso, L.A. Sazanov, Biochimica et Biophysica Acta - Bioenergetics 1857 (2016) 1777–1785.","mla":"Holt, Peter, et al. “Reversible FMN Dissociation from Escherichia Coli Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 11, Elsevier, 2016, pp. 1777–85, doi:10.1016/j.bbabio.2016.08.008."},"title":"Reversible FMN dissociation from Escherichia coli respiratory complex I","department":[{"_id":"LeSa"}],"author":[{"first_name":"Peter","last_name":"Holt","full_name":"Holt, Peter"},{"full_name":"Efremov, Rouslan","last_name":"Efremov","first_name":"Rouslan"},{"full_name":"Nakamaru Ogiso, Eiko","last_name":"Nakamaru Ogiso","first_name":"Eiko"},{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"publist_id":"6028"},{"abstract":[{"text":"Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536. kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95. Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.","lang":"eng"}],"acknowledgement":"funded by the Medical Research Council (Grant number MC_U105674180)","oa_version":"None","scopus_import":1,"quality_controlled":"1","publisher":"Elsevier","intvolume":" 1857","month":"07","publication_status":"published","year":"2016","publication":"Biochimica et Biophysica Acta - Bioenergetics","language":[{"iso":"eng"}],"day":"01","page":"892 - 901","date_created":"2018-12-11T11:52:30Z","issue":"7","date_published":"2016-07-01T00:00:00Z","doi":"10.1016/j.bbabio.2016.01.012","volume":1857,"_id":"1521","type":"journal_article","status":"public","date_updated":"2021-01-12T06:51:21Z","citation":{"ista":"Berrisford J, Baradaran R, Sazanov LA. 2016. Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 1857(7), 892–901.","chicago":"Berrisford, John, Rozbeh Baradaran, and Leonid A Sazanov. “Structure of Bacterial Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics. Elsevier, 2016. https://doi.org/10.1016/j.bbabio.2016.01.012.","ieee":"J. Berrisford, R. Baradaran, and L. A. Sazanov, “Structure of bacterial respiratory complex I,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 7. Elsevier, pp. 892–901, 2016.","short":"J. Berrisford, R. Baradaran, L.A. Sazanov, Biochimica et Biophysica Acta - Bioenergetics 1857 (2016) 892–901.","apa":"Berrisford, J., Baradaran, R., & Sazanov, L. A. (2016). Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. Elsevier. https://doi.org/10.1016/j.bbabio.2016.01.012","ama":"Berrisford J, Baradaran R, Sazanov LA. Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 2016;1857(7):892-901. doi:10.1016/j.bbabio.2016.01.012","mla":"Berrisford, John, et al. “Structure of Bacterial Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 7, Elsevier, 2016, pp. 892–901, doi:10.1016/j.bbabio.2016.01.012."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Berrisford, John","last_name":"Berrisford","first_name":"John"},{"last_name":"Baradaran","full_name":"Baradaran, Rozbeh","first_name":"Rozbeh"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"publist_id":"5654","department":[{"_id":"LeSa"}],"title":"Structure of bacterial respiratory complex I"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:52:10Z","citation":{"short":"L.A. Sazanov, Nature Reviews Molecular Cell Biology 16 (2015) 375–388.","ieee":"L. A. Sazanov, “A giant molecular proton pump: structure and mechanism of respiratory complex I,” Nature Reviews Molecular Cell Biology, vol. 16, no. 6. Nature Publishing Group, pp. 375–388, 2015.","apa":"Sazanov, L. A. (2015). A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. Nature Publishing Group. https://doi.org/10.1038/nrm3997","ama":"Sazanov LA. A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. 2015;16(6):375-388. doi:10.1038/nrm3997","mla":"Sazanov, Leonid A. “A Giant Molecular Proton Pump: Structure and Mechanism of Respiratory Complex I.” Nature Reviews Molecular Cell Biology, vol. 16, no. 6, Nature Publishing Group, 2015, pp. 375–88, doi:10.1038/nrm3997.","ista":"Sazanov LA. 2015. A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. 16(6), 375–388.","chicago":"Sazanov, Leonid A. “A Giant Molecular Proton Pump: Structure and Mechanism of Respiratory Complex I.” Nature Reviews Molecular Cell Biology. Nature Publishing Group, 2015. https://doi.org/10.1038/nrm3997."},"title":"A giant molecular proton pump: structure and mechanism of respiratory complex I","department":[{"_id":"LeSa"}],"author":[{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"publist_id":"5517","_id":"1638","status":"public","type":"journal_article","language":[{"iso":"eng"}],"publication":"Nature Reviews Molecular Cell Biology","day":"22","publication_status":"published","year":"2015","date_created":"2018-12-11T11:53:11Z","issue":"6","volume":16,"date_published":"2015-05-22T00:00:00Z","doi":"10.1038/nrm3997","page":"375 - 388","oa_version":"None","abstract":[{"text":"The mitochondrial respiratory chain, also known as the electron transport chain (ETC), is crucial to life, and energy production in the form of ATP is the main mitochondrial function. Three proton-translocating enzymes of the ETC, namely complexes I, III and IV, generate proton motive force, which in turn drives ATP synthase (complex V). The atomic structures and basic mechanisms of most respiratory complexes have previously been established, with the exception of complex I, the largest complex in the ETC. Recently, the crystal structure of the entire complex I was solved using a bacterial enzyme. The structure provided novel insights into the core architecture of the complex, the electron transfer and proton translocation pathways, as well as the mechanism that couples these two processes.","lang":"eng"}],"intvolume":" 16","month":"05","quality_controlled":"1","scopus_import":1,"publisher":"Nature Publishing Group"},{"author":[{"orcid":"0000-0002-9864-3586","full_name":"Letts, Jame A","last_name":"Letts","first_name":"Jame A","id":"322DA418-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov"}],"publist_id":"5465","title":"Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions","department":[{"_id":"LeSa"}],"date_updated":"2021-01-12T06:52:30Z","citation":{"ama":"Letts JA, Sazanov LA. Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. 2015;33(8):135-145. doi:10.1016/j.sbi.2015.08.008","apa":"Letts, J. A., & Sazanov, L. A. (2015). Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. Elsevier. https://doi.org/10.1016/j.sbi.2015.08.008","ieee":"J. A. Letts and L. A. Sazanov, “Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions,” Current Opinion in Structural Biology, vol. 33, no. 8. Elsevier, pp. 135–145, 2015.","short":"J.A. Letts, L.A. Sazanov, Current Opinion in Structural Biology 33 (2015) 135–145.","mla":"Letts, James A., and Leonid A. Sazanov. “Gaining Mass: The Structure of Respiratory Complex I-from Bacterial towards Mitochondrial Versions.” Current Opinion in Structural Biology, vol. 33, no. 8, Elsevier, 2015, pp. 135–45, doi:10.1016/j.sbi.2015.08.008.","ista":"Letts JA, Sazanov LA. 2015. Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. 33(8), 135–145.","chicago":"Letts, James A, and Leonid A Sazanov. “Gaining Mass: The Structure of Respiratory Complex I-from Bacterial towards Mitochondrial Versions.” Current Opinion in Structural Biology. Elsevier, 2015. https://doi.org/10.1016/j.sbi.2015.08.008."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","status":"public","_id":"1683","page":"135 - 145","date_created":"2018-12-11T11:53:27Z","volume":33,"doi":"10.1016/j.sbi.2015.08.008","issue":"8","date_published":"2015-08-01T00:00:00Z","year":"2015","publication_status":"published","language":[{"iso":"eng"}],"publication":"Current Opinion in Structural Biology","day":"01","quality_controlled":"1","scopus_import":1,"publisher":"Elsevier","intvolume":" 33","month":"08","abstract":[{"text":"The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.","lang":"eng"}],"oa_version":"None"}]