AMPylation of Rho GTPases by Vibrio VopS Disrupts Effector Binding and Downstream Signaling

AMPylation of Rho GTPases by Vibrio VopS Disrupts Effector Binding and Downstream Signaling
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DOI:
10.1126/science.1166382
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发表时间:
2009-01-09
期刊:
影响因子:
56.9
通讯作者:
Orth, Kim
Orth, Kim
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yarbrough, Melanie L.;Li, Yan;Orth, Kim

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副溶血性弧菌III型效应子VopS通过抑制Rho鸟苷三磷酸酶(GTP酶)而参与细胞变圆和肌动蛋白细胞骨架的崩溃。我们发现VopS可以用腺苷5 '-单磷酸(AMP)共价修饰Rho、Rac和Cdc 42上的保守苏氨酸残基。所产生的AMP化阻止了Rho GTP酶与下游效应物的相互作用,从而抑制了感染细胞中的肌动蛋白组装。真核蛋白质也直接修饰AMP,潜在地扩大了分子信号转导的翻译后修饰库。
The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases ( GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5 '- monophosphate ( AMP). The resulting AMPylation prevented the interaction of Rho GTPases with downstream effectors, thereby inhibiting actin assembly in the infected cell. Eukaryotic proteins were also directly modified with AMP, potentially expanding the repertoire of posttranslational modifications for molecular signaling.