A coiled coil trigger site is essential for rapid binding of synaptobrevin to the SNARE acceptor complex.

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Version: Final published version
Serval ID
serval:BIB_670CA2694D05
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A coiled coil trigger site is essential for rapid binding of synaptobrevin to the SNARE acceptor complex.
Journal
Journal of Biological Chemistry
Author(s)
Wiederhold K., Kloepper T.H., Walter A.M., Stein A., Kienle N., Sørensen J.B., Fasshauer D.
ISSN
1083-351X[electronic], 0021-9258[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
285
Number
28
Pages
21549-21559
Language
english
Abstract
Exocytosis from synaptic vesicles is driven by stepwise formation of a tight alpha-helical complex between the fusing membranes. The complex is composed of the three SNAREs: synaptobrevin 2, SNAP-25, and syntaxin 1a. An important step in complex formation is fast binding of vesicular synaptobrevin to the preformed syntaxin 1.SNAP-25 dimer. Exactly how this step relates to neurotransmitter release is not well understood. Here, we combined different approaches to gain insights into this reaction. Using computational methods, we identified a stretch in synaptobrevin 2 that may function as a coiled coil "trigger site." This site is also present in many synaptobrevin homologs functioning in other trafficking steps. Point mutations in this stretch inhibited binding to the syntaxin 1.SNAP-25 dimer and slowed fusion of liposomes. Moreover, the point mutations severely inhibited secretion from chromaffin cells. Altogether, this demonstrates that the trigger site in synaptobrevin is crucial for productive SNARE zippering.
Keywords
Amino Acid Motifs, Animals, Binding Sites, Calcium/chemistry, Calorimetry/methods, Chromaffin Cells/metabolism, Dimerization, Electrophysiology/methods, Liposomes/chemistry, Mice, Neurotransmitter Agents/metabolism, Point Mutation, Protein Structure, Tertiary, R-SNARE Proteins/chemistry, Rats, SNARE Proteins/chemistry
Pubmed
Web of science
Open Access
Yes
Create date
21/02/2011 13:07
Last modification date
20/08/2019 14:22
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