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

نویسندگان

  • Rory N Pruitt
  • Melissa G Chambers
  • Kenneth K-S Ng
  • Melanie D Ohi
  • D Borden Lacy
چکیده

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

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 107 30  شماره 

صفحات  -

تاریخ انتشار 2010