Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine

Gilles Flatau, Emmanuel Lemichez, Michel Gauthier, Pierre Chardin, Sonia Paris, Carla Fiorentini and Patrice Boquet ()
Additional contact information
Gilles Flatau: *INSERM U452, Faculté de Médecine, avenue de Valombrose
Emmanuel Lemichez: *INSERM U452, Faculté de Médecine, avenue de Valombrose
Michel Gauthier: *INSERM U452, Faculté de Médecine, avenue de Valombrose
Pierre Chardin: †Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, route des Lucioles
Sonia Paris: †Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, route des Lucioles
Carla Fiorentini: Istituto Superiore di Sanità
Patrice Boquet: *INSERM U452, Faculté de Médecine, avenue de Valombrose

Nature, 1997, vol. 387, issue 6634, 729-733

Abstract: Abstract 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 cells3,4. Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho4,5 and indirect evidence indicates that CNF1 might constitutively activate Rho6. 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.

Date: 1997
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DOI: 10.1038/42743

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