The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli.
The cytotoxic necrotizing factor 1, from uropathogenic Escherichia coli, is the paradigm of Rho-GTPases-activating bacterial toxins. CNF1 is a MW 108kDa A-B protein toxin divided into three domains which are implicated in the three steps of the intoxication process. The N-terminal domain contains the cell receptor function and binds with high affinity to a cell receptor not yet identified. Binding of the toxin is followed by its internalization by endocytosis and its transport into late endosomes. The middle toxin domain contains two hydophobic helices which allow translocation of the toxin across the membrane upon acidification in late endosomes. Finally the carboxy-terminal domain of CNF1 is an enzyme which deamidates Rho-GTP-binding proteins (Rho, Rac and Cdc42) glutamine 63 (for Rho) or glutamine 61 (for Rac and Cdc42). Deamidation of glutamine 63/61 blocks the intrinsic or the GTPase activating protein (GAP)-induced hydrolysis of GTP leading to the permanent activation of the GTPase. Activation of Rho GTPases by CNF1 induces a profound reorganization of the cell actin cytoskeleton. By its properties on Rho GTPases CNF1 is to date an invaluable tool for cell biology studies.
Boquet
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INSERM U452, Faculty of Medicine, 06107, Nice, France. boquet@unice.fr
D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D002477:Cells / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000235:genetics / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006801:Humans; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D001427:Bacterial Toxins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; C060296:cytotoxic necrotizing factor type 1; D020741:rho GTP-Binding Proteins