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PMID: 21499244 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Munc13 mediates the transition from the closed syntaxin-Munc18 complex to the SNARE complex.

Nature structural & molecular biology ·Vol. 18 ·No. 5 ·2011-05-00 ·Pages 542-9

Ma C, Li W, Xu Y, Rizo J

Abstract

During the priming step that leaves synaptic vesicles ready for neurotransmitter release, the SNARE syntaxin-1 transitions from a closed conformation that binds Munc18-1 tightly to an open conformation within the highly stable SNARE complex. Control of this conformational transition is important for brain function, but the underlying mechanism is unknown. NMR and fluorescence experiments now show that the Munc13-1 MUN domain, which plays a central role in vesicle priming, markedly accelerates the transition from the syntaxin-1-Munc18-1 complex to the SNARE complex. This activity depends on weak interactions of the MUN domain with the syntaxin-1 SNARE motif, and probably with Munc18-1. Together with available physiological data, these results provide a defined molecular basis for synaptic vesicle priming, and they illustrate how weak protein-protein interactions can play crucial biological roles by promoting transitions between high-affinity macromolecular assemblies.

MeSH Terms
Amino Acid Motifs Animals Binding Sites Fluorescence Resonance Energy Transfer Humans Munc18 Proteins/chemistry,metabolism Nerve Tissue Proteins/chemistry,metabolism,physiology Nuclear Magnetic Resonance, Biomolecular Protein Structure, Tertiary Rats SNARE Proteins/chemistry,metabolism,physiology Synaptosomal-Associated Protein 25/chemistry,metabolism Syntaxin 1/chemistry,metabolism Vesicle-Associated Membrane Protein 2/chemistry,metabolism
Chemicals
Munc18 Proteins Nerve Tissue Proteins SNAP25 protein, human SNARE Proteins Stxbp1 protein, rat Synaptosomal-Associated Protein 25 Syntaxin 1 Unc13a protein, rat Vamp2 protein, rat Vesicle-Associated Membrane Protein 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ma Cong
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Li Wei
Xu Yibin
Rizo Josep
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2047
Published
2011-05-00
Epub
2011-00-17
Pages
542-9
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3087822
Subset
IM
Grants
NINDS NIH HHS · R01 NS037200 · United States
NINDS NIH HHS · R01 NS037200-14 · United States
NINDS NIH HHS · NS37200 · United States
External Links
PubMed source DOI: 10.1038/nsmb.2047 PMC Full Text View journal details
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