title: Rho-glucosylating Clostridium difficile toxins A and B: new insights into structure and function.
abstract: Clostridium difficile causes pseudomembranous colitis and is responsible for many cases of nosocomial antibiotic-associated diarrhea. Major virulence factors of C. difficile are the glucosylating exotoxins A and B. Both toxins enter target cells in a pH- dependent manner from endosomes by forming pores. They translocate the N-terminal catalytic domains into the cytosol of host cells and inactivate Rho guanosine triphosphatases by glucosylation. The crystal structure of the catalytic domain of toxin B was solved in a complex with uridine diphosphate, glucose, and manganese ion, exhibiting a folding of type A family glycosyltransferases. Crystallization of fragments of the C-terminus of toxin A, which is characterized by polypeptide repeats, revealed a solenoid-like structure often found in bacterial cell surface proteins. These studies, which provide new insights into structure, uptake, and function of the family of clostridial glucosylating toxins, are reviewed.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jank
authors.forename: Torsten
authors.initials: T
authors.lastname: Giesemann
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism*; D005964:Glucosyltransferases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; C080487:Clostridium difficile enterotoxin A receptor; C417623:Clostridium difficile enterotoxin B receptor; C488583:Clostridium difficile lethal toxin B; D004768:Enterotoxins; D011971:Receptors, Immunologic; C041348:tcdA protein, Clostridium difficile; D005964:Glucosyltransferases; D020741:rho GTP-Binding Proteins