Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE
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DOI：
10.1093/emboj/cdf329
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发表时间：
2002-07-01
期刊：
影响因子：
11.4
通讯作者：
Scheffzek, K
中科院分区：
文献类型：
--
作者：
Buchwald, G;Friebel, A;Scheffzek, K
肠道致病菌鼠伤寒沙门氏菌利用III型分泌系统将细菌毒素注入宿主细胞胞质溶胶。这些毒素短暂激活Rho家族GTP结合蛋白依赖性信号级联反应，以诱导细胞骨架重排。这些被转运的沙门氏菌毒素之一SopE，尽管与Rho特异性真核鸟嘌呤核苷酸交换因子Dbl样蛋白缺乏序列相似性，但能够以类似Dbl的方式激活Cdc42。为了阐明SopE介导的鸟嘌呤核苷酸交换机制，我们分析了SopE的一个催化片段与Cdc42之间的复合物结构。SopE结合并锁定Cdc42的开关I和开关II区域，使其处于一种促进鸟嘌呤核苷酸释放的构象。这种构象与Rac1和真核Dbl样交换因子Tiam1形成的复合物中的构象惊人地相似。然而，SopE的催化结构域与Tiam1的结构完全不同，并且通过不同的氨基酸与开关区域相互作用。因此，SopE是第一个能够诱导Rho家族蛋白中鸟嘌呤核苷酸交换的非Dbl样蛋白的例子。
The bacterial enteropathogen Salmonella typhimurium employs a type III secretion system to inject bacterial toxins into the host cell cytosol. These toxins transiently activate Rho family GTP-binding protein-dependent signaling cascades to induce cytoskeletal rearrangements. One of these translocated Salmonella toxins, SopE, can activate Cdc42 in a Dbl-like fashion despite its lack of sequence similarity to Dbl-like proteins, the Rho-specific eukaryotic guanine nucleotide exchange factors. To elucidate the mechanism of SopE-mediated guanine nucleotide exchange, we have analyzed the structure of the complex between a catalytic fragment of SopE and Cdc42. SopE binds to and locks the switch I and switch II regions of Cdc42 in a conformation that promotes guanine nucleotide release. This conformation is strikingly similar to that of Rac1 in complex with the eukaryotic Dbl-like exchange factor Tiam1. However, the catalytic domain of SopE has an entirely different architecture from that of Tiam1 and interacts with the switch regions via different amino acids. Therefore, SopE represents the first example of a non-Dbl-like protein capable of inducing guanine nucleotide exchange in Rho family proteins.