Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-12
Yang, Xiaoyu
Wang, Shen
Sheng, Yi
Xu, Tao
Ma, Cong
Zhang, Mingshu
Zhang, Rongguang
Xu, Tao
Zou, Wenjuan
Kang, Lijun
Wu, Lijie
Zhang, Rongguang
Rizo, Josep
Xu, Tao
Abstract： 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 a-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. 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.
Peer Review Status:
Awaiting Review
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