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.
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期刊:
NATURE STRUCTURAL & MOLECULAR BIOLOGY
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分类:
生物学
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生物物理学
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生物物理、生物化学与分子生物学
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引用:
ChinaXiv:201605.01521
(或此版本
ChinaXiv:201605.01521V1)
DOI:10.12074/201605.01521V1
CSTR:32003.36.ChinaXiv.201605.01521.V1
- 推荐引用方式:
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.(2016).Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.NATURE STRUCTURAL & MOLECULAR BIOLOGY.[ChinaXiv:201605.01521]
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