Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College, London SW7 2AZ, United Kingdom.
Infect Immun. 2010 Apr;78(4):1417-25. doi: 10.1128/IAI.01250-09. Epub 2010 Feb 1.
Subversion of Rho family small GTPases, which control actin dynamics, is a common infection strategy used by bacterial pathogens. In particular, Salmonella enterica serovar Typhimurium, Shigella flexneri, enteropathogenic Escherichia coli (EPEC), and enterohemorrhagic Escherichia coli (EHEC) translocate type III secretion system (T3SS) effector proteins to modulate the Rho GTPases RhoA, Cdc42, and Rac1, which trigger formation of stress fibers, filopodia, and lamellipodia/ruffles, respectively. The Salmonella effector SopE is a guanine nucleotide exchange factor (GEF) that activates Rac1 and Cdc42, which induce "the trigger mechanism of cell entry." Based on a conserved Trp-xxx-Glu motif, the T3SS effector proteins IpgB1 and IpgB2 of Shigella, SifA and SifB of Salmonella, and Map of EPEC and EHEC were grouped together into a WxxxE family; recent studies identified the T3SS EPEC and EHEC effectors EspM and EspT as new family members. Recent structural and functional studies have shown that representatives of the WxxxE effectors share with SopE a 3-D fold and GEF activity. In this minireview, we summarize contemporary findings related to the SopE and WxxxE GEFs in the context of their role in subverting general host cell signaling pathways and infection.
Rho 家族小 GTPases 的颠覆，控制肌动蛋白动态，是细菌病原体常用的一种感染策略。特别是鼠伤寒沙门氏菌、福氏志贺菌、肠致病性大肠杆菌（EPEC）和肠出血性大肠杆菌（EHEC）将 III 型分泌系统（T3SS）效应蛋白易位到调节 Rho GTPases RhoA、Cdc42 和 Rac1，分别触发应力纤维、丝状伪足和片状伪足/皱襞的形成。沙门氏菌效应蛋白 SopE 是一种鸟嘌呤核苷酸交换因子（GEF），可激活 Rac1 和 Cdc42，引发“细胞进入的触发机制”。基于保守的 Trp-xxx-Glu 基序，Shigella 的 T3SS 效应蛋白 IpgB1 和 IpgB2、Salmonella 的 SifA 和 SifB 以及 EPEC 和 EHEC 的 Map 被归入 WxxxE 家族；最近的研究确定了 T3SS EPEC 和 EHEC 效应蛋白 EspM 和 EspT 为新的家族成员。最近的结构和功能研究表明，WxxxE 效应蛋白的代表与 SopE 具有 3D 折叠和 GEF 活性。在这篇简评中，我们总结了 SopE 和 WxxxE GEFs 在颠覆一般宿主细胞信号通路和感染方面的当代研究结果。
