6a30 | pdb_00006a30
Crystal Structure of Munc13-1 MUN Domain and Synaptobrevin-2 Juxtamembrane Linker Region
Structural highlights
Function[UN13A_RAT] Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Also involved in secretory granule priming in insulin secretion.[1] [2] [3] [VAMP2_RAT] Involved in the targeting and/or fusion of transport vesicles to their target membrane (By similarity). Publication Abstract from PubMedThe transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly. Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly.,Wang S, Li Y, Gong J, Ye S, Yang X, Zhang R, Ma C Nat Commun. 2019 Jan 8;10(1):69. doi: 10.1038/s41467-018-08028-6. PMID:30622273[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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