Structural highlights
Function
[STXB1_RAT] May participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May play a role in determining the specificity of intracellular fusion reactions.
Publication Abstract from PubMed
Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.
Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.,Wang X, Gong J, Zhu L, Wang S, Yang X, Xu Y, Yang X, Ma C EMBO J. 2020 Jul 9:e103631. doi: 10.15252/embj.2019103631. PMID:32643828[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang X, Gong J, Zhu L, Wang S, Yang X, Xu Y, Yang X, Ma C. Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly. EMBO J. 2020 Jul 9:e103631. doi: 10.15252/embj.2019103631. PMID:32643828 doi:http://dx.doi.org/10.15252/embj.2019103631
