Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine
Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine
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DOI：
10.1038/42743
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发表时间：
1997-06-12
期刊：
影响因子：
64.8
通讯作者：
Boquet, P
中科院分区：
文献类型：
--
作者：
Flatau, G;Lemichez, E;Boquet, P
致病性大肠杆菌可引起多种疾病，包括腹泻、溶血性尿毒综合征、肾脏感染、败血症、肺炎和脑膜炎。称为细胞毒性坏死因子（CNF）的毒素是由尿路致病性（CNF 1）（1）或肠道致病性（CNF 2）（2）E产生的毒力因子之一。分别导致人类和动物疾病的大肠杆菌菌株。CNF诱导培养细胞中肌动蛋白应力纤维和焦点接触的含量增加（3，4）。CNF对肌动蛋白细胞骨架的影响与GTP结合蛋白Rho电泳迁移率的降低相关（4，5），间接证据表明CNF 1可能组成性激活Rho（6）。在这里，我们表明，CNF1催化脱酰胺的谷氨酰胺残基在位置63的Rho，把它变成谷氨酸，抑制内在的GTP水解和刺激其GTP酶激活蛋白（GAP）。因此，CNF1对谷氨酰胺63的脱酰胺作用导致Rho的组成性激活，并诱导肌动蛋白应力纤维的重组。据我们所知，CNF1是第一个通过特定靶蛋白脱酰胺作用的细菌毒素的例子。
Pathogenic Escherichia coli are responsible for a variety of diseases, including diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the virulence factors produced by uropathogenic (CNF1)(1) or enteropathogenic (CNF2)(2) E. coli strains that cause diseases in humans and animals, respectively. CNFs induce an increase in the content of actin stress fibres and focal contacts in cultured cells(3,4). Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho(4,5) and indirect evidence indicates that CNF1 might constitutively activate Rho(6). Here we show that CNF1 catalyses the deamidation of a glutamine residue at position 63 of Rho, turning it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the reorganization of actin stress fibres. To our knowledge, CNF1 is the first example of a bacterial toxin acting by deamidation of a specific target protein.