Structure and function of longin SNAREs
Structure and function of longin SNAREs
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DOI：
10.1242/jcs.178574
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发表时间：
2015-12-01
影响因子：
4
通讯作者：
Tareste, David
中科院分区：
文献类型：
--
作者：
Daste, Frederic;Galli, Thierry;Tareste, David
可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白构成了细胞内转运和细胞间通讯的核心膜融合机制。十多年前，有人提出SNARE的一个子集的长N-末端结构域（以下称为longin结构域）可能是膜运输中具有多种功能的关键调节因子。结构、生物化学和细胞生物学研究现在已经产生了大量的数据支持这一假设，并表明长蛋白结构域在调节SNARE的分选和活性中的作用。在这里，我们回顾了第一个十年的结构功能数据的三个原型longin陷阱：Ykt 6，VAMP 7和Sec 22 b。我们将特别强调保守的分子机制，使长蛋白结构域折叠回融合诱导陷阱卷曲螺旋结构域，从而抑制膜融合，并描述了长蛋白陷阱与调节其细胞内分选的蛋白质的相互作用。长蛋白结构域在调节SNARE的膜定位和膜融合活性中的这种双重功能表明其作为细胞内运输的关键调节模块的作用。
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core membrane fusion machinery of intracellular transport and intercellular communication. A little more than ten years ago, it was proposed that the long N-terminal domain of a subset of SNAREs, henceforth called the longin domain, could be a crucial regulator with multiple functions in membrane trafficking. Structural, biochemical and cell biology studies have now produced a large set of data that support this hypothesis and indicate a role for the longin domain in regulating the sorting and activity of SNAREs. Here, we review the first decade of structure-function data on the three prototypical longin SNAREs: Ykt6, VAMP7 and Sec22b. We will, in particular, highlight the conserved molecular mechanisms that allow longin domains to fold back onto the fusion-inducing SNARE coiled-coil domain, thereby inhibiting membrane fusion, and describe the interactions of longin SNAREs with proteins that regulate their intracellular sorting. This dual function of the longin domain in regulating both the membrane localization and membrane fusion activity of SNAREs points to its role as a key regulatory module of intracellular trafficking.