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PMID: 18275821 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex.

Structure (London, England : 1993) ·Vol. 16 ·No. 2 ·2008-02-00 ·Pages 308-20

Weninger K, Bowen ME, Choi UB, Chu S, Brunger AT

Abstract

Syntaxin/SNAP-25 interactions precede assembly of the ternary SNARE complex that is essential for neurotransmitter release. This binary complex has been difficult to characterize by bulk methods because of the prevalence of a 2:1 dead-end species. Here, using single-molecule fluorescence, we find the structure of the 1:1 syntaxin/SNAP-25 binary complex is variable, with states changing on the second timescale. One state corresponds to a parallel three-helix bundle, whereas other states show one of the SNAP-25 SNARE domains dissociated. Adding synaptobrevin suppresses the dissociated helix states. Remarkably, upon addition of complexin, Munc13, Munc18, or synaptotagmin, a similar effect is observed. Thus, the 1:1 binary complex is a dynamic acceptor for synaptobrevin binding, and accessory proteins stabilize this acceptor. In the cellular environment the binary complex is actively maintained in a configuration where it can rapidly interact with synaptobrevin, so formation is not likely a limiting step for neurotransmitter release.

MeSH Terms
Fluorescence Resonance Energy Transfer Lipid Bilayers/metabolism Protein Structure, Tertiary Qa-SNARE Proteins/chemistry,metabolism R-SNARE Proteins/metabolism SNARE Proteins/metabolism Synaptosomal-Associated Protein 25/chemistry,metabolism
Chemicals
Lipid Bilayers Qa-SNARE Proteins R-SNARE Proteins SNARE Proteins Synaptosomal-Associated Protein 25
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Weninger Keith
Department of Physics, North Carolina State University, Raleigh, NC 27695-8202, USA.
Bowen Mark E
Choi Ucheor B
Chu Steven
Brunger Axel T
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
0969-2126
DOI
10.1016/j.str.2007.12.010
Published
2008-02-00
Pages
308-20
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2856644
Subset
IM
Grants
NIMH NIH HHS · MH63105 · United States
NIMH NIH HHS · R01 MH081923 · United States
NIMH NIH HHS · R01 MH081923-01 · United States
NIMH NIH HHS · R37 MH063105 · United States
NIMH NIH HHS · R01 MH063105-09 · United States
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH063105 · United States
Corrections
CommentIn
PMID: 18275808
External Links
PubMed source DOI: 10.1016/j.str.2007.12.010 PMC Full Text View journal details
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