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

许多细菌病原体利用T3SS装置将毒力蛋白（T3SS效应物）注入宿主细胞，从而操纵宿主细胞的细胞功能。结构建模分析和生化实验表明，T3SS分泌中的底物选择和识别机制与AAA+蛋白酶clpxp -底物相互作用系统相似。在此基础上，将结构性能分析集成到效应器预测系统中，进一步提高了预测精度。对程序中列出的9种沙门氏菌效应物进行实验验证，证实STM1239等5种新型效应物可分泌到培养基上清液中。

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.