Munc18-1 binds directly to the neuronal SNARE complex
Munc18-1 binds directly to the neuronal SNARE complex
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DOI：
10.1073/pnas.0611318104
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发表时间：
2007-02-20
影响因子：
11.1
通讯作者：
Rizo, Josep
中科院分区：
文献类型：
--
作者：
Dulubova, Irina;Khvotchev, Mikhail;Rizo, Josep
SM蛋白（Sec 1/Munc 18样蛋白）和SNARE蛋白（可溶性NSF附着蛋白受体）对于细胞内膜融合是必不可少的，但它们功能之间的一般偶联机制尚不清楚，部分原因是已经描述了不同的SM蛋白/SNARE结合模式。在突触囊泡胞吐过程中，SM蛋白Munc 18 -1已知与SNARE蛋白syntaxin-1紧密结合，但仅当syntaxin-1处于与SNARE复合物形成不相容的闭合构象时。我们现在表明，Munc 18 -1也紧密结合组装SNARE复合物含有syntaxin-1。新发现的Munc 18 -1/SNARE复合物相互作用涉及Munc 18 -1与syntaxin-1的N-末端H-abc结构域和组装的SNARE复合物的四螺旋束的接触。与早期的研究一起，我们的研究结果表明，Munc 18 -1与封闭的syntaxin-1的结合是一种专门化，其进化以满足神经元胞吐的严格监管要求，而Munc 18 -1与组装的SNARE复合物的结合反映了SM蛋白参与执行膜融合的一般功能。
Both SM proteins (for Sec1/Munc18-like proteins) and SNARE proteins (for soluble NSF-attachment protein receptors) are essential for intracellular membrane fusion, but the general mechanism of coupling between their functions is unclear, in part because diverse SM protein/SNARE binding modes have been described. During synaptic vesicle exocytosis, the SM protein Munc18-1 is known to bind tightly to the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conformation that is incompatible with SNARE complex formation. We now show that Munc18-1 also binds tightly to assembled SNARE complexes containing syntaxin-1. The newly discovered Munc18-1/SNARE complex interaction involves contacts of Munc18-1 with the N-terminal H-abc domain of syntaxin-1 and the four-helical bundle of the assembled SNARE complex. Together with earlier studies, our results suggest that binding of Munc18-1 to closed syntaxin-1 is a specialization that evolved to meet the strict regulatory requirements of neuronal exocytosis, whereas binding of Munc18-1 to assembled SNARE complexes reflects a general function of SM proteins involved in executing membrane fusion.