7UDB

Cryo-EM structure of a synaptobrevin-Munc18-1-syntaxin-1 complex class 2

Summary for 7UDB

• Entry DOI: 10.2210/pdb7udb/pdb
• EMDB information: 26455
• Descriptor: Syntaxin-binding protein 1, Syntaxin-1A, Synaptobrevin-2 (3 entities in total)
• Functional Keywords: munc18, syntaxin, synaptobrevin, snare, membrane fusion, neurotransmitter release, exocytosis
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 3
• Total formula weight: 104581.81

Authors

Rizo, J.,Bai, X.,Stepien, K.P.,Xu, J.,Zhang, X. (deposition date: 2022-03-18, release date: 2022-04-06, Last modification date: 2024-10-23)

Primary citation

Stepien, K.P.,Xu, J.,Zhang, X.,Bai, X.C.,Rizo, J.
SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex.
Sci Adv, 8:eabo5272-eabo5272, 2022

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 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.

PubMed: 35731863
DOI: 10.1126/sciadv.abo5272

Experimental method

ELECTRON MICROSCOPY (3.5 Å)