Rho-glucosylating Clostridium difficile toxins A and B: new insights into structure and function.
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.
Jank
Thomas
T
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany.
Giesemann
Torsten
T
Aktories
Klaus
K
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*
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