SNX16 Regulates the Recycling of E-Cadherin through a Unique Mechanism of Coordinated Membrane and Cargo Binding
SNX16 Regulates the Recycling of E-Cadherin through a Unique Mechanism of Coordinated Membrane and Cargo Binding
复制标题
SNX16 通过协调膜和货物结合的独特机制调节 E-钙粘蛋白的回收
DOI：
10.1016/j.str.2017.06.015
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发表时间：
2017-08-01
期刊：
影响因子：
5.7
通讯作者：
Liu, Jinsong
中科院分区：
文献类型：
--
作者：
Xu, Jinxin;Zhang, Leilei;Liu, Jinsong
E-钙粘蛋白是细胞表面粘附连接的主要成分。SNX 16是分选连接蛋白的独特成员，其包含PX结构域下游的卷曲螺旋（CC）结构域。我们在这里报告，SNX 16调节E-钙粘蛋白的回收贩运。我们解析了SNX 16的PX-CC单元的晶体结构，揭示了一种独特的剪切型同源二聚体。我们在SNX 16中鉴定了一个新的PI 3 P结合口袋，其由PX和CC结构域组成。令人惊讶的是，我们发现PPII/α 2环，这通常被认为是PX家族蛋白的膜插入环，参与E-钙粘蛋白与SNX 16的结合。然后，我们提出了SNX 16的多价膜结合模型。我们的研究假设了一种新的机制，协调膜结合和货物结合的SNX家族蛋白一般，并提供新的见解E-钙粘蛋白的回收贩运。
E-Cadherin is a major component of adherens junctions on cell surfaces. SNX16 is a unique member of sorting nexins that contains a coiled-coil (CC) domain downstream of the PX domain. We report here that SNX16 regulates the recycling trafficking of E-cadherin. We solved the crystal structure of PX-CC unit of SNX16 and revealed a unique shear shaped homodimer. We identified a novel PI3P binding pocket in SNX16 that consists of both the PX and the CC domains. Surprisingly, we showed that the PPII/alpha 2 loop, which is generally regarded as a membrane insertion loop in PX family proteins, is involved in the E-cadherin binding with SNX16. We then proposed a multivalent membrane binding model for SNX16. Our study postulates a new mechanism for coordinated membrane binding and cargo binding for SNX family proteins in general, and provide novel insights into recycling trafficking of E-cadherin.