Sec17/Sec18 act twice, enhancing membrane fusion and then disassembling cis-SNARE complexes

  1. Hongki Song
  2. Amy S Orr
  3. Mengtong Duan
  4. Alexey J Merz
  5. William T Wickner  Is a corresponding author
  1. Geisel School of Medicine at Dartmouth, United States
  2. University of Washington, United States

Abstract

At physiological protein levels, the slow HOPS- and SNARE-dependent fusion which occurs upon complete SNARE zippering is stimulated by Sec17 and Sec18:ATP without requiring ATP hydrolysis. To stimulate, Sec17 needs its central residues which bind the 0-layer of the SNARE complex and its N-terminal apolar loop. Adding a transmembrane anchor to the N-terminus of Sec17 bypasses this requirement for apolarity of the Sec17 loop, suggesting that the loop functions for membrane binding rather than to trigger bilayer rearrangement. In contrast, when complete C-terminal SNARE zippering is prevented, fusion strictly requires Sec18 and Sec17, and the Sec17 apolar loop has functions beyond membrane anchoring. Thus Sec17 and Sec18 act twice in the fusion cycle, binding to trans-SNARE complexes to accelerate fusion, then hydrolyzing ATP to disassemble cis-SNARE complexes.

Article and author information

Author details

  1. Hongki Song

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amy S Orr

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mengtong Duan

    Departments of Biochemistry and Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexey J Merz

    Departments of Biochemistry and Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2177-6492
  5. William T Wickner

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    William.T.Wickner@dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8431-0468

Funding

National Institutes of Health (R01 GM23377-40)

  • William T Wickner

National Institutes of Health (R35GM118037-01)

  • William T Wickner

National Institutes of Health (GM077349)

  • Alexey J Merz

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

Reviewing Editor

  1. Axel T Brunger, Stanford University Medical Center, United States

Publication history

  1. Received: March 8, 2017
  2. Accepted: July 17, 2017
  3. Accepted Manuscript published: July 18, 2017 (version 1)
  4. Version of Record published: August 2, 2017 (version 2)

Copyright

© 2017, Song 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. Hongki Song
  2. Amy S Orr
  3. Mengtong Duan
  4. Alexey J Merz
  5. William T Wickner
(2017)
Sec17/Sec18 act twice, enhancing membrane fusion and then disassembling cis-SNARE complexes
eLife 6:e26646.
https://doi.org/10.7554/eLife.26646

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