Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3
Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3
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DOI：
10.1074/jbc.m109.096966
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发表时间：
2010-04-02
影响因子：
4.8
通讯作者：
Dominguez, Roberto
中科院分区：
文献类型：
--
作者：
Baek, Kyuwon;Knoedler, Andreas;Dominguez, Roberto
外泌囊是一种进化上保守的八聚体复合物，参与从酵母到人类的极化胞吐作用。胞吐的Sec 3亚基通过其结合磷脂和小GTP酶的能力作为胞吐的空间地标。Sec 3的N-末端结构域（Sec 3 N）的结构从头开始确定，并且定义了普列克底物蛋白同源（PH）结构域的新亚类沿着携带该结构域的蛋白质的新家族。PH结构域Sec 3 N的N-和C-末端分别呈现额外的α-螺旋和两条β-链，其通过结构域交换介导二聚化。该结构鉴定了负责磷脂结合的残基，当在细胞中突变时，其损害胞吐组分在质膜上的定位并导致胞吐缺陷。Sec 3的PH结构域通过其结合小的GTdR Cdc 42和磷脂的能力，在质膜上起到符合检测器的作用。
The exocyst is an evolutionarily conserved octameric complex involved in polarized exocytosis from yeast to humans. The Sec3 subunit of the exocyst acts as a spatial landmark for exocytosis through its ability to bind phospholipids and small GTPases. The structure of the N-terminal domain of Sec3 (Sec3N) was determined ab initio and defines a new subclass of pleckstrin homology (PH) domains along with a new family of proteins carrying this domain. Respectively, N- and C-terminal to the PH domain Sec3N presents an additional alpha-helix and two beta-strands that mediate dimerization through domain swapping. The structure identifies residues responsible for phospholipid binding, which when mutated in cells impair the localization of exocyst components at the plasma membrane and lead to defects in exocytosis. Through its ability to bind the small GTPase Cdc42 and phospholipids, the PH domain of Sec3 functions as a coincidence detector at the plasma membrane.