Structural Basis of the Proteolytic and Chaperone Activity of Chlamydia trachomatis CT441
Structural Basis of the Proteolytic and Chaperone Activity of Chlamydia trachomatis CT441
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DOI：
10.1128/jb.02140-14
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Hansen, Guido
中科院分区：
文献类型：
--
作者：
Kohlmann, Friedrich;Shima, Kensuke;Hansen, Guido
沙眼衣原体是世界范围内可预防性失明的最常见原因，也是女性感染性不孕的主要原因。几种细菌因素与C的发病机制有关。沙眼结合结构和突变分析，我们已经表明，CT 441的蛋白水解功能依赖于一个保守的丝氨酸/赖氨酸/谷氨酰胺催化三联体和一个功能性底物结合位点内的灵活PDZ（突触后密度为95 kDa，光盘大，和小带occludens）域。以前，已经表明CT 441参与调节宿主细胞的雌激素信号传导应答。我们的研究结果表明，虽然在体外CT 441表现出对SRAP 1，雌激素受体α的共激活剂，CT 441介导的SRAP 1降解的蛋白水解活性在细胞内发育周期中观察不到宿主细胞裂解和感染性衣原体释放之前。最令人信服的是，我们新发现了CT 441的分子伴侣活性，表明CT 441在原核蛋白质质量控制过程中的作用。
Chlamydia trachomatis is the most prevalent cause of preventable blindness worldwide and a major reason for infectious infertility in females. Several bacterial factors have been implicated in the pathogenesis of C. trachomatis. Combining structural and mutational analysis, we have shown that the proteolytic function of CT441 depends on a conserved Ser/Lys/Gln catalytic triad and a functional substrate-binding site within a flexible PDZ (postsynaptic density of 95 kDa, discs large, and zonula occludens) domain. Previously, it has been suggested that CT441 is involved in modulating estrogen signaling responses of the host cell. Our results show that although in vitro CT441 exhibits proteolytic activity against SRAP1, a coactivator of estrogen receptor alpha, CT441-mediated SRAP1 degradation is not observed during the intracellular developmental cycle before host cells are lysed and infectious chlamydiae are released. Most compellingly, we have newly identified a chaperone activity of CT441, indicating a role of CT441 in prokaryotic protein quality control processes.