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| Title | SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex. |
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| Journal, issue, pages | Sci Adv, Vol. 8, Issue 25, Page eabo5272, Year 2022 |
| Publish date | Jun 24, 2022 |
 Authors | Karolina P Stepien / Junjie Xu / Xuewu Zhang / Xiao-Chen Bai / Josep Rizo /  |
| PubMed Abstract | Munc18-1 forms a template to organize assembly of the neuronal SNARE complex that triggers neurotransmitter release, binding first to a closed conformation of syntaxin-1 where its amino-terminal ...Munc18-1 forms a template to organize assembly of the neuronal SNARE complex that triggers neurotransmitter release, binding first to a closed conformation of syntaxin-1 where its amino-terminal region interacts with the SNARE motif, and later binding to synaptobrevin. However, the mechanism of SNARE complex assembly remains unclear. Here, we report two cryo-EM structures of Munc18-1 bound to cross-linked syntaxin-1 and synaptobrevin. The structures allow visualization of how syntaxin-1 opens and reveal how part of the syntaxin-1 amino-terminal region can help nucleate interactions between the amino termini of the syntaxin-1 and synaptobrevin SNARE motifs, while their carboxyl termini bind to distal sites of Munc18-1. These observations, together with mutagenesis, SNARE complex assembly experiments, and fusion assays with reconstituted proteoliposomes, support a model whereby these interactions are critical to initiate SNARE complex assembly and multiple energy barriers enable diverse mechanisms for exquisite regulation of neurotransmitter release. |
 External links | Sci Adv / PubMed:35731863 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.5 - 3.7 Å |
| Structure data | EMDB-26455, PDB-7udb: EMDB-26456, PDB-7udc: |
| Source |
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 Keywords |  EXOCYTOSIS / Munc18 / syntaxin / synaptobrevin / SNARE / membrane fusion / neurotransmitter release |
