Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
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DOI：
10.7554/elife.22311
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发表时间：
2017-02-22
期刊：
影响因子：
7.7
通讯作者：
Collins, Brett M.
中科院分区：
文献类型：
--
作者：
Paul, Blessy;Kim, Hyun Sung;Collins, Brett M.
在感染过程中，衣原体病原体形成一个细胞内膜结合的复制生态位，称为包涵体，其中富含细菌跨膜蛋白，称为Incs。Inc结合并操纵宿主细胞蛋白以促进包涵体扩增并提供针对先天免疫应答的伪装。通常在内体膜运输中起作用的分选连接蛋白（SNX）蛋白是主要类别的包涵体相关宿主蛋白，并且被因斯/CT 116募集。与因斯复合的SNX 5 phox同源（PX）结构域的晶体结构定义了这些相互作用的精确分子基础。结合位点是SNX 5和相关家族成员SNX 6和SNX 32所独有的。有趣的是，该位点在整个进化过程中在SNX 5同源物中也是保守的，这表明因斯通过模拟天然宿主蛋白质相互作用来捕获SNX 5相关蛋白。因此，这些发现提供了第一个机制的见解，无论是衣原体Incs如何劫持宿主蛋白质，以及SNX 5相关的PX结构域如何作为蛋白质复合物组装的支架。
During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions. The binding site is unique to SNX5 and related family members SNX6 and SNX32. Intriguingly the site is also conserved in SNX5 homologues throughout evolution, suggesting that IncE captures SNX5-related proteins by mimicking a native host protein interaction. These findings thus provide the first mechanistic insights both into how chlamydial Incs hijack host proteins, and how SNX5-related PX domains function as scaffolds in protein complex assembly.