Bacterial Toxins Inhibiting or Activating Small GTP‐Binding Proteins
- 1 December 1999
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 886 (1) , 83-90
- https://doi.org/10.1111/j.1749-6632.1999.tb09403.x
Abstract
Amino acids located on the switch 1 or switch 2 domains of small GTPases of the Ras and Rho family are targets of several bacterial toxins. Exoenzyme C3 from Clostridium botulinum ADP‐ribosylates specifically Rho at R43 and prevents the recruitment of Rho on the cell membrane. This blocks the downstream effects of the Rho GTPase. However, exoenzyme C3 is not a toxin, and chimeric proteins fusing C3 with the B moiety of either diphtheria toxin or Pseudomonas aeruginosa exotoxin A have been produced to intoxicate cells with low concentration of C3. C. difficile toxin B modifies by glucosylation Rho on T37 and Rac and Cdc42 on T35. Glucosylation of Rho, Rac, and Cdc42 blocks the binding of these GTPases on their downstream effectors. C. sordellii lethal toxin modifies Ras, Rap, and Rac on T35 by glucosylation. Cytotoxic necrotizing factor 1 (CNF1), from uropathogenic Escherichia coli strains, deamidates Q63 of Rho into E63, thereby blocking the intrinsic or GAP‐mediated GTPase of Rho. This allows permanent activation of Rho. Thus, Rho GTPases are targets for three different toxin activities. Molecular mechanisms of these toxins are discussed.Keywords
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