Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE.
Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE.
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分类 nexin 5/6 与细菌效应器 IncE 相互作用的结构和功能见解
DOI：
10.1038/sigtrans.2017.30
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发表时间：
2017
影响因子：
39.3
通讯作者：
Jia D
中科院分区：
文献类型：
--
作者：
Sun Q;Yong X;Sun X;Yang F;Dai Z;Gong Y;Zhou L;Zhang X;Niu D;Dai L;Liu JJ;Jia D
内体运输途径是许多细胞活动所必需的。它们也是许多细胞内病原体的重要靶点。内体转运的关键调控因子包括反转录复合体和分选连接蛋白（SNXs）。沙眼衣原体效应蛋白IncE直接靶向逆转录体组分SNX5和SNX6并抑制逆转录体介导的转运，但其确切机制尚不清楚。我们展示了SNX5与IncE配合物的PX结构域的晶体结构，表明IncE与SNX5高度保守的疏水沟槽结合。SNX5/6独特的螺旋发夹对结合至关重要，这解释了SNX5/6对IncE的特异性。SNX5/6-IncE相互作用是IncE的细胞定位及其抑制功能所必需的。从机制上讲，IncE抑制CI-MPR货物与含有逆转录物的内体亚域的关联。我们的研究为逆转录物介导的运输调控提供了新的见解，并阐明了宿主和病原体之间在控制细胞运输方面的复杂竞争。
The endosomal trafficking pathways are essential for many cellular activities. They are also important targets by many intracellular pathogens. Key regulators of the endosomal trafficking include the retromer complex and sorting nexins (SNXs). Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport, but the exact mechanism has remained unclear. We present the crystal structure of the PX domain of SNX5 in complex with IncE, showing that IncE binds to a highly conserved hydrophobic groove of SNX5. The unique helical hairpin of SNX5/6 is essential for binding, explaining the specificity of SNX5/6 for IncE. The SNX5/6–IncE interaction is required for cellular localization of IncE and its inhibitory function. Mechanistically, IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains. Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking.
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影响因子：
30.3
作者：
Mirrashidi KM;Elwell CA;Verschueren E;Johnson JR;Frando A;Von Dollen J;Rosenberg O;Gulbahce N;Jang G;Johnson T;Jäger S;Gopalakrishnan AM;Sherry J;Dunn JD;Olive A;Penn B;Shales M;Cox JS;Starnbach MN;Derre I;Valdivia R;Krogan NJ;Engel J
通讯作者：
Engel J
SNX6 的消融导致 CA1 锥体神经元突触功能和空间记忆缺陷
影响因子：
7.7
作者：
Niu, Yang;Dai, Zhanghua;Liu, Jia-Jia
通讯作者：
Liu, Jia-Jia
影响因子：
4
作者：
Seaman, Matthew N. J.
通讯作者：
Seaman, Matthew N. J.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.3
作者：
Jia D;Gomez TS;Billadeau DD;Rosen MK
通讯作者：
Rosen MK