Paul Blessy, Kim Hyun Sung, Kerr Markus C, Huston Wilhelmina M, Teasdale Rohan D, Collins Brett M
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia.
School of Life Sciences, University of Technology Sydney, Sydney, Australia.
Elife. 2017 Feb 22;6:e22311. doi: 10.7554/eLife.22311.
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.
在感染过程中，衣原体病原体形成一种称为包涵体的细胞内膜结合复制龛，其中富含称为Incs的细菌跨膜蛋白。Incs结合并操纵宿主细胞蛋白以促进包涵体扩展，并提供针对先天免疫反应的伪装。通常在内体膜运输中起作用的分选连接蛋白（SNX）是一类主要的与包涵体相关的宿主蛋白，由Ince/CT116招募。与Ince复合的SNX5 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SNX5以及相关家族成员SNX6和SNX32所特有的。有趣的是，该位点在整个进化过程中的SNX5同源物中也保守，这表明Ince通过模拟天然宿主蛋白相互作用来捕获SNX5相关蛋白。因此，这些发现首次提供了关于衣原体Incs如何劫持宿主蛋白以及SNX5相关PX结构域如何在蛋白质复合物组装中作为支架发挥作用的机制见解。
