The accessory helix of complexin functions by stabilizing central helix secondary structure
- Weill Cornell Medical College, United States
- 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
Reviewing Editor
- Graeme W Davis, University of California, San Francisco, United States
Version history
- Received: September 10, 2014
- Accepted: November 7, 2014
- Accepted Manuscript published: November 10, 2014 (version 1)
- 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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The accessory helix of complexin functions by stabilizing central helix secondary structure
eLife 3:e04553.
https://doi.org/10.7554/eLife.04553
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