---
_id: '12138'
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.'
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
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).
article_processing_charge: No
article_type: original
author:
- first_name: Vladyslav
  full_name: Kravchuk, Vladyslav
  id: 4D62F2A6-F248-11E8-B48F-1D18A9856A87
  last_name: Kravchuk
- first_name: Olga
  full_name: Petrova, Olga
  id: 5D8C9660-5D49-11EA-8188-567B3DDC885E
  last_name: Petrova
- first_name: Domen
  full_name: Kampjut, Domen
  id: 37233050-F248-11E8-B48F-1D18A9856A87
  last_name: Kampjut
- first_name: Anna
  full_name: Wojciechowska-Bason, Anna
  last_name: Wojciechowska-Bason
- first_name: Zara
  full_name: Breese, Zara
  last_name: Breese
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
citation:
  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>
  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>
  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>.
  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.
  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.” <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.
date_created: 2023-01-12T12:04:33Z
date_published: 2022-09-22T00:00:00Z
date_updated: 2023-08-04T08:54:52Z
day: '22'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41586-022-05199-7
ec_funded: 1
external_id:
  isi:
  - '000854788200001'
  pmid:
  - '36104567'
file:
- access_level: open_access
  checksum: d42a93e24f59e883ef0b5429832391d0
  content_type: application/pdf
  creator: lsazanov
  date_created: 2023-05-30T17:05:31Z
  date_updated: 2023-05-30T17:05:31Z
  file_id: '13104'
  file_name: EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf
  file_size: 1425655
  relation: main_file
  success: 1
- access_level: open_access
  checksum: 5422bc0a73b3daadafa262c7ea6deae3
  content_type: application/pdf
  creator: lsazanov
  date_created: 2023-05-30T17:07:05Z
  date_updated: 2023-05-30T17:07:05Z
  file_id: '13105'
  file_name: EcCxI_manuscript_rev3_SI_All_opt_upd.pdf
  file_size: 9842513
  relation: main_file
  success: 1
file_date_updated: 2023-05-30T17:07:05Z
has_accepted_license: '1'
intvolume: '       609'
isi: 1
issue: '7928'
keyword:
- Multidisciplinary
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 808-814
pmid: 1
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
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41586-022-05457-8
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/proton-dominos-kick-off-life/
  record:
  - id: '12781'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: A universal coupling mechanism of respiratory complex I
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 609
year: '2022'
...