1. Structural Biology and Molecular Biophysics
  2. Cell Biology

Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins

  1. Sylvain Zorman
  2. Aleksander A Rebane
  3. Lu Ma
  4. Guangcan Yang
  5. Matthew A Molski
  6. Jeff Coleman
  7. Frederic Pincet
  8. James E Rothman
  9. Yongli Zhang  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. Yale University, United States
  3. UMR CNRS 8550 Associée aux Universités Paris 6 et Paris 7, Ecole Normale Supérieure, France
https://doi.org/10.7554/eLife.03348
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  1. Sylvain Zorman
  2. Aleksander A Rebane
  3. Lu Ma
  4. Guangcan Yang
  5. Matthew A Molski
  6. Jeff Coleman
  7. Frederic Pincet
  8. James E Rothman
  9. Yongli Zhang
(2014)
Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins
eLife 3:e03348.
https://doi.org/10.7554/eLife.03348
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Abstract

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are evolutionarily conserved machines that couple their folding/assembly to membrane fusion. However, it is unclear how these processes are regulated and function. To determine these mechanisms, we characterized the folding energy and kinetics of four representative SNARE complexes at a single-molecule level using high-resolution optical tweezers. We found that all SNARE complexes assemble by the same step-wise zippering mechanism: slow N-terminal domain (NTD) association, a pause in a force-dependent half-zippered intermediate and fast C-terminal domain (CTD) zippering. The energy release from CTD zippering differs for yeast (13 kBT) and neuronal SNARE complexes (27 kBT), and is concentrated at the C-terminal part of CTD zippering. Thus, SNARE complexes share a conserved zippering pathway and polarized energy release to efficiently drive membrane fusion, but generate different amounts of zippering energy to regulate fusion kinetics.

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Author details

  1. Sylvain Zorman

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Aleksander A Rebane

    Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Lu Ma

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Guangcan Yang

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Matthew A Molski

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Jeff Coleman

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Frederic Pincet

    UMR CNRS 8550 Associée aux Universités Paris 6 et Paris 7, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  8. James E Rothman

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Yongli Zhang

    Yale University School of Medicine, New Haven, United States
    For correspondence
    yongli.zhang@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Version history

  1. Received: May 13, 2014
  2. Accepted: August 29, 2014
  3. Accepted Manuscript published: September 1, 2014 (version 1)
  4. Version of Record published: September 18, 2014 (version 2)

Copyright

© 2014, Zorman 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. Sylvain Zorman
  2. Aleksander A Rebane
  3. Lu Ma
  4. Guangcan Yang
  5. Matthew A Molski
  6. Jeff Coleman
  7. Frederic Pincet
  8. James E Rothman
  9. Yongli Zhang
(2014)
Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins
eLife 3:e03348.
https://doi.org/10.7554/eLife.03348

Share this article

https://doi.org/10.7554/eLife.03348

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