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RESEARCH PRODUCT
Glucosylation of Rho proteins by Clostridium difficile toxin B.
Ingo JustMatthias MannJörg SelzerKlaus AktoriesC. Von Eichel-streiberMatthias Wilmsubject
ThreonineRHOAGlycosylationBacterial ToxinsMolecular Sequence DataClostridium difficile toxin AClostridium difficile toxin Bmacromolecular substancesmedicine.disease_causeMicrofilamentCatalysisMass SpectrometryGTP PhosphohydrolasesBacterial ProteinsGTP-Binding ProteinsmedicineTumor Cells CulturedAnimalsAmino Acid SequenceCytoskeletonActinCells CulturedCytoskeletonMultidisciplinarybiologyToxinClostridioides difficileActin cytoskeletonActinsRecombinant ProteinsRatsGlucoseMarsupialiaBiochemistryGlucosyltransferasesbiology.proteinrhoA GTP-Binding Proteindescription
TOXIN A and B, the major virulence factors of Clostridium difficile, are the causative agents of antibiotic-associated pseudomembran-ous colitis. In cultured cell lines their potent cytotoxicity results from their ability to induce disaggregation of the microfilament cytoskeleton1,2. Toxin B acts on the low-molecular-mass GTPase Rho A3,4, which is involved in the regulation of the actin cytoskeleton. We report here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid thre-onine at position 37. The modification was identified and localized by tandem electrospray mass spectrometry. UDP-glucose selectively serves as cosubstrate for the monoglucosylation reaction catalysed by toxin B. Microinjection of RhoA previously glucosyl-ated by toxin B into monolayer cells caused disaggregation of actin filaments, indicating a dominant-negative activity of glucosylated RhoA.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1995-06-08 | Nature |