Modulation of host signaling by a bacterial mimic:: structure of the Salmonella effector SptP bound to Rac1
Modulation of host signaling by a bacterial mimic:: structure of the Salmonella effector SptP bound to Rac1
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DOI：
10.1016/s1097-2765(00)00141-6
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发表时间：
2000-12-01
期刊：
影响因子：
16
通讯作者：
Galán, JE
中科院分区：
文献类型：
--
作者：
Stebbins, CE;Galán, JE
沙门氏菌利用一种特殊的蛋白质分泌系统将一系列效应蛋白输送到宿主细胞中。这些效应物中的一些刺激Cdc42和rad依赖的细胞骨架变化，促进细菌内化。这些潜在的细胞毒性改变被效应物SptP迅速逆转，SptP是一种酪氨酸磷酸酶和GTPase激活蛋白（GAP），靶向Cdc42和Rac1。SptP-Rac1过渡态复合物的2.3埃分辨率晶体结构揭示了一个不寻常的GAP结构，模仿宿主的功能同源物。磷酸酶结构域具有保守的活性位点，但具有明显的表面性质。与Rad的结合诱导了与GTPase的Switch I和Switch II区域广泛接触的四螺旋束的SptP的显著稳定。
Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effecters stimulate Cdc42- and Rad-dependent cytoskeletal changes that promote bacterial internalization. These potentially cytotoxic alterations are rapidly reversed by the effector SptP, a tyrosine phosphatase and GTPase activating protein (GAP) that targets Cdc42 and Rac1. The 2.3 Angstrom resolution crystal structure of an SptP-Rac1 transition state complex reveals an unusual GAP architecture that mimics host functional homologs. The phosphatase domain possesses a conserved active site but distinct surface properties. Binding to Rad induces a dramatic stabilization in SptP of a four-helix bundle that makes extensive contacts with the Switch I and Switch II regions of the GTPase.