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PMID: 19571812 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Helical extension of the neuronal SNARE complex into the membrane.

Nature ·Vol. 460 ·No. 7254 ·2009-07-23 ·Pages 525-8

Stein A, Weber G, Wahl MC, Jahn R

Abstract

Neurotransmission relies on synaptic vesicles fusing with the membrane of nerve cells to release their neurotransmitter content into the synaptic cleft, a process requiring the assembly of several members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. SNAREs represent an evolutionarily conserved protein family that mediates membrane fusion in the secretory and endocytic pathways of eukaryotic cells. On membrane contact, these proteins assemble in trans between the membranes as a bundle of four alpha-helices, with the energy released during assembly being thought to drive fusion. However, it is unclear how the energy is transferred to the membranes and whether assembly is conformationally linked to fusion. Here, we report the X-ray structure of the neuronal SNARE complex, consisting of rat syntaxin 1A, SNAP-25 and synaptobrevin 2, with the carboxy-terminal linkers and transmembrane regions at 3.4 A resolution. The structure shows that assembly proceeds beyond the already known core SNARE complex, resulting in a continuous helical bundle that is further stabilized by side-chain interactions in the linker region. Our results suggest that the final phase of SNARE assembly is directly coupled to membrane merger.

MeSH Terms
Animals Crystallography, X-Ray Membrane Proteins/chemistry Mice Models, Molecular Neurons/metabolism Protein Stability Protein Structure, Quaternary Rats SNARE Proteins/chemistry,metabolism Synapses/metabolism Syntaxin 1/chemistry Transition Temperature Vesicle-Associated Membrane Protein 2/chemistry
Chemicals
Membrane Proteins SNARE Proteins Syntaxin 1 Vesicle-Associated Membrane Protein 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Stein Alexander
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Weber Gert
Wahl Markus C
Jahn Reinhard
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature08156
Published
2009-07-23
Epub
2009-00-01
Pages
525-8
Language
English
Region
England
NLM ID
0410462
PMCID
PMC3108252
Subset
IM
Grants
NIGMS NIH HHS · P01 GM072694 · United States
NIGMS NIH HHS · P01 GM072694-01 · United States
External Links
PubMed source DOI: 10.1038/nature08156 PMC Full Text View journal details
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