{"status":"public","related_material":{"record":[{"status":"public","id":"12781","relation":"dissertation_contains"}],"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"}]},"quality_controlled":"1","title":"A universal coupling mechanism of respiratory complex I","date_created":"2023-01-12T12:04:33Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Submitted Version","oa":1,"scopus_import":"1","publisher":"Springer Nature","issue":"7928","date_published":"2022-09-22T00:00:00Z","publication_status":"published","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."}],"department":[{"_id":"LeSa"}],"day":"22","type":"journal_article","file":[{"checksum":"d42a93e24f59e883ef0b5429832391d0","relation":"main_file","creator":"lsazanov","access_level":"open_access","file_name":"EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf","content_type":"application/pdf","date_updated":"2023-05-30T17:05:31Z","date_created":"2023-05-30T17:05:31Z","file_size":1425655,"success":1,"file_id":"13104"},{"relation":"main_file","checksum":"5422bc0a73b3daadafa262c7ea6deae3","file_name":"EcCxI_manuscript_rev3_SI_All_opt_upd.pdf","access_level":"open_access","creator":"lsazanov","content_type":"application/pdf","date_updated":"2023-05-30T17:07:05Z","date_created":"2023-05-30T17:07:05Z","file_size":9842513,"file_id":"13105","success":1}],"date_updated":"2023-08-04T08:54:52Z","pmid":1,"article_processing_charge":"No","month":"09","keyword":["Multidisciplinary"],"isi":1,"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).","file_date_updated":"2023-05-30T17:07:05Z","project":[{"name":"Structural characterization of E. coli complex I: an important mechanistic model","_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E","grant_number":"25541"},{"call_identifier":"H2020","grant_number":"101020697","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","name":"Structure and mechanism of respiratory chain molecular machines"}],"ddc":["572"],"volume":609,"intvolume":"       609","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"year":"2022","article_type":"original","citation":{"ieee":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, and L. A. Sazanov, “A universal coupling mechanism of respiratory complex I,” <i>Nature</i>, vol. 609, no. 7928. Springer Nature, pp. 808–814, 2022.","mla":"Kravchuk, Vladyslav, et al. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>, vol. 609, no. 7928, Springer Nature, 2022, pp. 808–14, doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>.","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. <i>Nature</i>. 2022;609(7928):808-814. doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>","chicago":"Kravchuk, Vladyslav, Olga Petrova, Domen Kampjut, Anna Wojciechowska-Bason, Zara Breese, and Leonid A Sazanov. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>.","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.","apa":"Kravchuk, V., Petrova, O., Kampjut, D., Wojciechowska-Bason, A., Breese, Z., &#38; Sazanov, L. A. (2022). A universal coupling mechanism of respiratory complex I. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>"},"ec_funded":1,"_id":"12138","language":[{"iso":"eng"}],"publication":"Nature","has_accepted_license":"1","author":[{"id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","full_name":"Kravchuk, Vladyslav","first_name":"Vladyslav","last_name":"Kravchuk"},{"full_name":"Petrova, Olga","id":"5D8C9660-5D49-11EA-8188-567B3DDC885E","last_name":"Petrova","first_name":"Olga"},{"full_name":"Kampjut, Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","first_name":"Domen","last_name":"Kampjut"},{"full_name":"Wojciechowska-Bason, Anna","first_name":"Anna","last_name":"Wojciechowska-Bason"},{"full_name":"Breese, Zara","last_name":"Breese","first_name":"Zara"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","first_name":"Leonid A"}],"page":"808-814","doi":"10.1038/s41586-022-05199-7","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"external_id":{"isi":["000854788200001"],"pmid":["36104567"]}}