Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.
Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.
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MUN 结构域打开突触融合蛋白是 Munc13 在突触小泡启动中发挥作用的基础
DOI：
10.1038/nsmb.3038
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发表时间：
2015-07
影响因子：
16.8
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Yang X;Wang S;Sheng Y;Zhang M;Zou W;Wu L;Kang L;Rizo J;Zhang R;Xu T;Ma C
β-13-Munc 13通过其MUN结构域在突触囊泡启动中发挥重要作用。然而，目前尚不清楚这种功能是否源于MUN结构域在体外介导从Munc 18 -1-封闭型突触融合蛋白-1复合物向SNARE复合物转变的能力。大鼠Munc 13 -1 MUN结构域的晶体结构现在显示出由α-螺旋束形成的伸长的拱形结构，中间具有高度保守的疏水口袋。该口袋中两个残基（NF）的突变消除了Munc 13 -1 MUN结构域对SNARE复合物组装和体外SNARE依赖性蛋白脂质体融合的刺激。此外，在C.神经肌肉接头这些结果有力地支持了这样的观点，即syntaxin-1开放和SNARE复合物组装的编排是突触囊泡启动中β-13-Munc 13的核心作用的基础。
UNC-13-Munc13s play 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 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 C. elegans neuromuscular junctions. These results strongly 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.