Lipid-Induced Conformational Switch Controls Fusion Activity of Longin Domain SNARE Ykt6
Lipid-Induced Conformational Switch Controls Fusion Activity of Longin Domain SNARE Ykt6
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脂质诱导的构象转换控制 Longin 结构域 SNARE Ykt6 的融合活性
DOI：
10.1016/j.molcel.2010.01.024
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发表时间：
2010-02-12
期刊：
影响因子：
16
通讯作者：
Zhang, Mingjie
中科院分区：
文献类型：
--
作者：
Wen, Wenyu;Yu, Jiang;Zhang, Mingjie
虽然大多数SNARE通过其跨膜结构域永久锚定在膜上，但双重脂化的SNARE Ykt6在细胞内膜和细胞质中均存在。胞质Ykt6是无活性的，这是由于它们通过其longin结构域对SNARE核心的自抑制，尽管这种抑制的分子基础是未知的。在这里，我们证明了去脂Ykt6采用多种构象，在封闭状态下的人口很少。与脂肪酸复合的Ykt6的结构表明，在法尼基化后，Ykt6陷阱核心形成四个α螺旋，其缠绕在长蛋白结构域周围，形成占主导地位的闭合构象。脂肪酸，埋在一个疏水沟之间形成的Longin域和SNARE核心，是必不可少的维持Ykt6的自抑制构象。我们的研究表明，postpertinationally连接法呢基基团可以积极调节Ykt6融合活性，除了其预期的膜锚定作用。
While most SNAREs are permanently anchored to membranes by their transmembrane domains, the dually lipidated SNARE Ykt6 is found both on intracellular membranes and in the cytosol. The cytosolic Ykt6 is inactive due to them autoinhibition of the SNARE core by its longin domain, although the molecular basis of this inhibition is unknown. Here, we demonstrate that unlipidated Ykt6 adopts multiple conformations, with a small population in the closed state. The structure of Ykt6 in complex with a fatty acid suggests that, upon farnesylation, the Ykt6 SNARE core forms four alpha helices that wrap around the longin domain, forming a dominantly closed conformation. The fatty acid, buried in a hydrophobic groove formed between the longin domain and its SNARE core, is essential for maintaining the autoinhibited conformation of Ykt6. Our study reveals that the posttranslationally attached farnesyl group can actively regulate Ykt6 fusion activity in addition to its anticipated membrane-anchoring role.