Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming
Journal Article
·
· Nature Structural & Molecular Biology
- Huazhong Univ. of Science and Technology, Wuhan (China)
- Chinese Academy of Sciences (CAS), Beijing (China)
- Zhejiang Univ., Hangzhou (China)
- Chinese Academy of Sciences (CAS), Shanghai (China)
- Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
- Chinese Academy of Sciences (CAS), Beijing (China); Chinese Academy of Sciences (CAS), Shanghai (China)
- Huazhong Univ. of Science and Technology, Wuhan (China); Chinese Academy of Sciences (CAS), Beijing (China); Univ. of Chinese Academy of Sciences, Beijing (China)
UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1–closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. Here, these results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Key Basic Research Program of China; National Science Foundation of China; U.S. National Inst. of Health
- OSTI ID:
- 1259896
- Journal Information:
- Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 7 Vol. 22; ISSN 1545-9993
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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