Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 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

摘要： 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.

同行评议状态:待评议

 点击量 12379  下载量 2362  评论