Large clostridial cytotoxins: cellular biology of Rho/Ras-glucosylating toxins

Biochim Biophys Acta. 2004 Jul 6;1673(1-2):66-74. doi: 10.1016/j.bbagen.2004.03.014.

Abstract

Mono-O-glycosylation of eukaryotic target proteins is the molecular mechanism of bacterial protein toxins of the family of large clostridial cytotoxins. This toxin family encompasses several high molecular mass proteins (>250 kDa) of various Clostridia species that are implicated in severe human diseases. Toxin A and toxin B from Clostridium difficile are the causative agents of pseudomembranous colitis and antibiotic-associated diarrhea. Lethal toxin and hemorrhagic toxin from Clostridium sordellii as well as alpha-toxin from Clostridium novyi are involved in the gas gangrene syndrome. The common mode of action of large clostridial cytotoxins is elicited by specific glycosylation of small GTP-binding proteins in the cytosol of target cells using activated nucleotide sugars as cosubstrates. Specific modification at a single threonine residue in the small GTPases renders these important key players of various signaling pathways inactive. This minireview intends to give an overview on structure-function analysis and mode of action of the large clostridial cytotoxins, as well as on the resulting functional consequences of glycosylation of target proteins.

Publication types

  • Review

MeSH terms

  • Bacterial Proteins*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism*
  • Clostridium / metabolism*
  • Clostridium / pathogenicity
  • Cytotoxins / chemistry
  • Cytotoxins / metabolism*
  • Enterotoxins / metabolism
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / microbiology
  • Glycosylation
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / metabolism
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / metabolism

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Cytotoxins
  • Enterotoxins
  • tcdA protein, Clostridium difficile
  • toxB protein, Clostridium difficile
  • ras Proteins
  • rho GTP-Binding Proteins