Conformational change of syntaxin linker region induced by Munc13s initiates SNARE complex formation in synaptic exocytosis |
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| Authors: | Shen Wang Cong Ma Shen Wang Ucheor B Choi Jihong Gong Xiaoyu Yang Yun Li Austin L Wang Xiaofei Yang Axel T Brunger Cong Ma |
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| Affiliation: | 1. Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China;2. Key Laboratory of Cognitive Science, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, College of Life Science, South-Central University for Nationalities, Wuhan, China;3. Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA |
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| 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 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. |
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| Keywords: | Munc13 Munc18 neurotransmitter release synaptic vesicle fusion syntaxin |
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