Elucidation of structural mechanism of substrate selection and secretion signal in T3SS secretion by theoretical and experimental structural biology

许多细菌病原体通过使用T3SS装置将毒力蛋白(T3SS效应物)注射到宿主细胞中来操纵宿主细胞的细胞功能。结构模型分析和生化实验表明，T3SS分泌中底物的选择和识别的机制与AAA酶ClpXP-底物相互作用系统中的机制相似。在此基础上，将结构特性分析融入到效应器预测系统中，进一步提高了预测精度。对该程序列出的9个可能的沙门氏菌效应物的实验验证表明，包括STM1239在内的5个新的效应物被证实分泌到培养上清液中。

Many bacterial pathogens manipulate cellular functions of host cells by injecting virulence proteins(T3SS effectors) into host cells using T3SS apparatus. Structural modeling analysis and biochemical experiments revealed that substrate selection and the recognition in T3SS secretion are conducted by the similar mechanism as used in the system of AAA+ protease ClpXP-substrate interaction. Based on the findings, structural property analysis was integrated into the effector prediction system, and the prediction accuracy was further improved. Experimental validation for 9 putative Salmonella effectors listed by this program revealed that five novel effectors including STM1239 were confirmed to secrete into supernatant of culture media.