Structural organization of the functional domains of Clostridium difficile toxins A and B

• DOI: 10.1073/pnas.1002199107
• Publication Date: 2010-07-13T03:40:19Z
• Authors: Rory N. Pruitt; Melissa G. Chambers; Kenneth K.-S. Ng; Melanie D. Ohi; D. Borden Lacy
• Keywords: Glucosyltransferases; Glucosyltransferases

Clostridium difficile toxins A and B are members of an important class virulence factors known as large clostridial (LCTs). Toxin action involves four major steps: receptor-mediated endocytosis, translocation a catalytic glucosyltransferase domain across the membrane, release enzymatic moiety by autoproteolytic processing, glucosyltransferase-dependent inactivation Rho family proteins. We have imaged toxin (TcdA) (TcdB) holotoxins negative stain electron microscopy to show that these molecules similar in structure. then determined 3D structure for TcdA mapped organization its functional domains. The molecule has “pincher-like” head corresponding delivery two tails, long short, receptor-binding domains, respectively. second structure, obtained at acidic pH endosome, reveals significant structural change thus provides framework understanding molecular mechanism LCT cellular intoxication.