5ue8
From Proteopedia
The crystal structure of Munc13-1 C1C2BMUN domain
Structural highlights
FunctionUN13A_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] Publication Abstract from PubMedMunc13-1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13-1 are coordinated. The crystal structure of a Munc13-1 fragment including its C1, C2B and MUN domains (C1C2BMUN) reveals a 19.5 nm-long multi-helical structure with the C1 and C2B domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca2+-binding sites of the C1 and C2B domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13-1 by Ca2+ and diacylglycerol during short-term presynaptic plasticity are closely interrelated. Electrophysiological experiments in mouse neurons support the functional importance of the domain interfaces observed in C1C2BMUN. The structure imposes key constraints for models of neurotransmitter release and suggests that Munc13-1 bridges the vesicle and plasma membranes from the periphery of the membrane-membrane interface. Mechanistic Insights into Neurotransmitter Release and Presynaptic Plasticity from the Crystal Structure of Munc13-1 C1C2BMUN.,Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, Pan YZ, Ma C, Tomchick DR, Rosenmund C, Rizo J Elife. 2017 Feb 8;6. pii: e22567. doi: 10.7554/eLife.22567. PMID:28177287[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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