Conformational Change of Syntaxin Linker Region Induced by Munc13s Initiates SNARE Complex Formation in Synaptic Exocytosis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2017 Feb 1

PMID 28137749

Citations 59

Authors

Shen Wang

Ucheor B Choi

Jihong Gong

Xiaoyu Yang

Yun Li

Austin L Wang

Xiaofei Yang

Axel T Brunger

Cong Ma

Affiliations

Soon will be listed here.

Abstract

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1 adopts a closed conformation when bound to Munc18-1, preventing binding to synaptobrevin-2 and SNAP-25 to form the ternary SNARE complex. Although it is known that the MUN domain of Munc13-1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular mechanism is unclear. Here, we identified two conserved residues (R151, I155) in the syntaxin-1 linker region as key sites for the MUN domain interaction. This interaction is essential for SNARE complex formation and synaptic vesicle priming in neuronal cultures. Moreover, this interaction is important for a tripartite Munc18-1/syntaxin-1/MUN complex, in which syntaxin-1 still adopts a closed conformation tightly bound to Munc18-1, whereas the syntaxin-1 linker region changes its conformation, similar to that of the LE mutant of syntaxin-1 when bound to Munc18-1. We suggest that the conformational change of the syntaxin-1 linker region induced by Munc13-1 initiates ternary SNARE complex formation in the neuronal system.

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