The accessory helix of complexin functions by stabilizing central helix secondary structure

  1. Daniel T Radoff
  2. Yongming Dong
  3. David Snead
  4. Jihong Bai
  5. David Eliezer
  6. Jeremy S Dittman  Is a corresponding author
  1. Weill Cornell Medical College, United States
  2. Fred Hutchinson Cancer Research Center, United States

Abstract

The presynaptic protein complexin (CPX) is a critical regulator of synaptic vesicle fusion, but the mechanisms underlying its regulatory effects are not well understood. Its highly conserved central helix (CH) directly binds the ternary SNARE complex and is required for all known CPX functions. The adjacent accessory helix (AH) is not conserved despite also playing an important role in CPX function, and numerous models for its mechanism have been proposed. We examined the impact of AH mutations and chimeras on CPX function in vivo and in vitro using C. elegans. The mouse AH fully restored function when substituted into worm CPX suggesting its mechanism is evolutionarily conserved. CPX inhibitory function was impaired when helix propagation into the CH was disrupted whereas replacing the AH with a non-native helical sequence restored CPX function. We propose that the AH operates by stabilizing CH secondary structure rather than through protein or lipid interactions.

Article and author information

Author details

  1. Daniel T Radoff

    Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yongming Dong

    Fred Hutchinson Cancer Research Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David Snead

    Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jihong Bai

    Fred Hutchinson Cancer Research Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. David Eliezer

    Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeremy S Dittman

    Weill Cornell Medical College, New York, United States
    For correspondence
    jed2019@med.cornell.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Version history

  1. Received: September 10, 2014
  2. Accepted: November 7, 2014
  3. Accepted Manuscript published: November 10, 2014 (version 1)
  4. Version of Record published: December 10, 2014 (version 2)

Copyright

© 2014, Radoff 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. Daniel T Radoff
  2. Yongming Dong
  3. David Snead
  4. Jihong Bai
  5. David Eliezer
  6. Jeremy S Dittman
(2014)
The accessory helix of complexin functions by stabilizing central helix secondary structure
eLife 3:e04553.
https://doi.org/10.7554/eLife.04553

Share this article

https://doi.org/10.7554/eLife.04553

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