Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly
Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly
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DOI：
10.1038/nsmb954
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发表时间：
2005-07-01
影响因子：
16.8
通讯作者：
Owen, DJ
中科院分区：
文献类型：
--
作者：
Collins, BM;Skinner, CF;Owen, DJ
逆转录复合物负责将甘露糖6-磷酸受体从内体系统回收到高尔基体。在这里，我们提出的哺乳动物retromer亚基mVps 29的晶体结构，并表明它具有结构相似的二价金属含磷酸酯酶。mVps 29可以以类似的方式配位金属，但在体外没有可检测的磷酸酯酶活性，这表明了独特的特异性或功能。mVps 29和mVps 26亚基独立地结合mVps 35，并一起形成高亲和力的异源三聚体亚复合物。突变揭示了mVps 29与mVps 35相互作用以及随后与体内内体膜相关的结构基础。不同于主要Vps 35 p结合位点的保守疏水表面介导Vps 29 p-Vps 26 p-Vps 35 p亚复合物与酵母中的分选连接蛋白的组装，并且任一位点的突变导致逆转录酶依赖性膜运输的缺陷。
The retromer complex is responsible for the retrieval of mannose 6-phosphate receptors from the endosomal system to the Golgi. Here we present the crystal structure of the mammalian retromer subunit mVps29 and show that it has structural similarity to divalent metal-containing phosphoesterases. mVps29 can coordinate metals in a similar manner but has no detectable phosphoesterase activity in vitro, suggesting a unique specificity or function. The mVps29 and mVps26 subunits bind independently to mVps35 and together form a high-affinity heterotrimeric subcomplex. Mutagenesis reveals the structural basis for the interaction of mVps29 with mVps35 and subsequent association with endosomal membranes in vivo. A conserved hydrophobic surface distinct from the primary Vps35p binding site mediates assembly of the Vps29p - Vps26p - Vps35p subcomplex with sorting nexins in yeast, and mutation of either site results in a defect in retromer-dependent membrane trafficking.