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Conformational change of syntaxin linker region induced by Munc13s initiates SNARE complex formation in synaptic exocytosis
Author(s) -
Wang Shen,
Choi Ucheor B,
Gong Jihong,
Yang Xiaoyu,
Li Yun,
Wang Austin L,
Yang Xiaofei,
Brunger Axel T,
Ma Cong
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695775
Subject(s) - syntaxin , snare complex , synaptobrevin , syntaxin 3 , munc 18 , stx1a , biology , microbiology and biotechnology , ternary complex , linker , exocytosis , synaptic vesicle , biophysics , biochemistry , vesicle , secretion , membrane , enzyme , computer science , operating system
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 in vitro 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.