Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM

  1. Anna Zhou
  2. Alexis Rohou
  3. Daniel G Schep
  4. John V Bason
  5. Martin G Montgomery
  6. John E Walker
  7. Nikolaus Grigorieff
  8. John L Rubinstein  Is a corresponding author
  1. University of Toronto, Canada
  2. Janelia Research Campus, Howard Hughes Medical Institute, United States
  3. Medical Research Council, United Kingdom

Abstract

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted F0 region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the F0 region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the F0 region support a Brownian ratchet mechanism for proton-translocation driven rotation in ATP synthases.

Article and author information

Author details

  1. Anna Zhou

    The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Alexis Rohou

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel G Schep

    The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. John V Bason

    MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Martin G Montgomery

    MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. John E Walker

    MRC Mitochondrial Biology Unit, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Nikolaus Grigorieff

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. John L Rubinstein

    The Hospital for Sick Children, University of Toronto, Toronto, Canada
    For correspondence
    john.rubinstein@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Stephen C Harrison, Harvard Medical School, United States

Version history

  1. Received: July 21, 2015
  2. Accepted: October 5, 2015
  3. Accepted Manuscript published: October 6, 2015 (version 1)
  4. Version of Record published: December 7, 2015 (version 2)

Copyright

© 2015, Zhou et al.

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. Anna Zhou
  2. Alexis Rohou
  3. Daniel G Schep
  4. John V Bason
  5. Martin G Montgomery
  6. John E Walker
  7. Nikolaus Grigorieff
  8. John L Rubinstein
(2015)
Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM
eLife 4:e10180.
https://doi.org/10.7554/eLife.10180

Share this article

https://doi.org/10.7554/eLife.10180

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    Funding:

    This work was supported by the Weizmann Krenter Foundation and the Weizmann – Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.