1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Structural basis of proton translocation and force generation in mitochondrial ATP synthase

  1. Niklas Klusch
  2. Bonnie J Murphy
  3. Deryck J Mills
  4. Özkan Yildiz
  5. Werner Kühlbrandt  Is a corresponding author
  1. Max Planck Institute of Biophysics, Germany
Research Article
  • Cited 35
  • Views 4,683
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Cite this article as: eLife 2017;6:e33274 doi: 10.7554/eLife.33274

Abstract

ATP synthases produce ATP by rotary catalysis, powered by the electrochemical proton gradient across the membrane. Understanding this fundamental process requires an atomic model of the proton pathway. We determined the structure of an intact mitochondrial ATP synthase dimer by electron cryo-microscopy at near-atomic resolution. Charged and polar residues of the a-subunit stator define two aqueous channels, each spanning one half of the membrane. Passing through a conserved membrane-intrinsic helix hairpin, the lumenal channel protonates an acidic glutamate in the c-ring rotor. Upon ring rotation, the protonated glutamate encounters the matrix channel and deprotonates. An arginine between the two channels prevents proton leakage. The steep potential gradient over the sub-nm inter-channel distance exerts a force on the deprotonated glutamate, resulting in net directional rotation.

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Author details

  1. Niklas Klusch

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  2. Bonnie J Murphy

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6341-9368
  3. Deryck J Mills

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  4. Özkan Yildiz

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3659-2805
  5. Werner Kühlbrandt

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    For correspondence
    werner.kuehlbrandt@biophys.mpg.de
    Competing interests
    Werner Kühlbrandt, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2013-4810

Funding

Max-Planck-Gesellschaft

  • Niklas Klusch
  • Bonnie J Murphy
  • Deryck J Mills
  • Özkan Yildiz
  • Werner Kühlbrandt

Deutsche Forschungsgemeinschaft

  • Niklas Klusch
  • Werner Kühlbrandt

European Molecular Biology Organization

  • Bonnie J Murphy

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

Reviewing Editor

  1. Sjors HW Scheres, MRC Laboratory of Molecular Biology,, United Kingdom

Publication history

  1. Received: November 1, 2017
  2. Accepted: December 5, 2017
  3. Accepted Manuscript published: December 6, 2017 (version 1)
  4. Version of Record published: December 29, 2017 (version 2)

Copyright

© 2017, Klusch 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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