Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation

  1. Piotr Kolata
  2. Rouslan G Efremov  Is a corresponding author
  1. VIB-VUB, Belgium

Abstract

Respiratory complex I is a multi-subunit membrane protein complex that reversibly couples NADH oxidation and ubiquinone reduction with proton translocation against trans-membrane potential. Complex I from Escherichia coli is among the best functionally characterized complexes, but its structure remains unknown, hindering further mechanistic studies to understand the enzyme coupling mechanism. Here we describe the single particle cryo-electron microscopy (cryo-EM) structure of the entire catalytically active E. coli complex I reconstituted into lipid nanodiscs. The structure of this mesophilic bacterial complex I displays highly dynamic connection between the peripheral and membrane domains. The peripheral domain assembly is stabilized by unique terminal extensions and an insertion loop. The membrane domain structure reveals novel dynamic features. Unusual conformation of the conserved interface between the peripheral and membrane domains suggests an uncoupled conformation of the complex. Considering constraints imposed by the structural data we suggest a new simple hypothetical coupling mechanism for the molecular machine.

Data availability

Cryo-EM density maps and atomic models are deposited into the PDB and EMDB databases with the following accession codes: cytoplasmic domain (PDB ID: 7NZ1, EMD-12661), membrane domain (PDB ID: 7NYH, EMD-12652), entire complex conformation 1 (PDB ID: 7NYR, EMD-12653), conformation 2 (PDB ID: 7NYU,EMD-12654), conformation 3 (PDB ID: 7NYV, EMD-12655).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Piotr Kolata

    VIB Center for Structural Biology, VUB Structural Biology Brussels, VIB-VUB, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9484-5025
  2. Rouslan G Efremov

    VIB Center for Structural Biology, VUB Structural Biology Brussels, VIB-VUB, Brussels, Belgium
    For correspondence
    rouslan.efremov@vub.vib.be
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7516-8658

Funding

Fonds Wetenschappelijk Onderzoek (G0H5916N)

  • Rouslan G Efremov

Fonds Wetenschappelijk Onderzoek (G.0266.15N)

  • Rouslan G Efremov

H2020 European Research Council (726436)

  • Rouslan G Efremov

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: March 23, 2021
  2. Preprint posted: April 10, 2021 (view preprint)
  3. Accepted: July 23, 2021
  4. Accepted Manuscript published: July 26, 2021 (version 1)
  5. Accepted Manuscript updated: July 27, 2021 (version 2)
  6. Version of Record published: August 11, 2021 (version 3)

Copyright

© 2021, Kolata & Efremov

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Piotr Kolata
  2. Rouslan G Efremov
(2021)
Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation
eLife 10:e68710.
https://doi.org/10.7554/eLife.68710

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