1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation

  1. William John Allen
  2. Robin Adam Corey
  3. Peter Oatley
  4. Richard Barry Sessions
  5. Sheena E Radford
  6. Roman Tuma
  7. Ian Collinson  Is a corresponding author
  1. University of Bristol, United Kingdom
  2. University of Leeds, United Kingdom
Research Article
  • Cited 48
  • Views 4,167
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Cite this article as: eLife 2016;5:e15598 doi: 10.7554/eLife.15598

Abstract

The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor-protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY-channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids.

Article and author information

Author details

  1. William John Allen

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Robin Adam Corey

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Peter Oatley

    Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Richard Barry Sessions

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Sheena E Radford

    AStbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Roman Tuma

    Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Ian Collinson

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    For correspondence
    ian.collinson@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Ramanujan S Hegde, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: February 26, 2016
  2. Accepted: May 14, 2016
  3. Accepted Manuscript published: May 16, 2016 (version 1)
  4. Version of Record published: June 14, 2016 (version 2)
  5. Version of Record updated: June 28, 2016 (version 3)

Copyright

© 2016, Allen 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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