Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily proteins.
Infect Immun
; 79(2): 905-10, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21098103
ABSTRACT
Clostridium perfringens TpeL belongs to a family of large clostridial cytotoxins that encompasses Clostridium difficile toxin A (TcdA) and B (TcdB) and Clostridium sordellii lethal toxin (TcsL). We report here the identification of the TpeL-catalyzed modification of small GTPases. A recombinant protein (TpeL1-525) derived from the TpeL N-terminal catalytic domain in the presence of streptolysin O (SLO) induced the rounding of Vero cells and the glycosylation of cellular Rac1. Among several hexoses tested, UDP-N-acetyl-glucosamine (UDP-GlcNAc) and UDP-glucose (UDP-Glc) served as cosubstrates for TpeL1-525-catalyzed modifications. TpeL1-525 catalyzed the incorporation of UDP-Glc into Ha-Ras, Rap1B, and RalA and of UDP-GlcNAc into Rac1, Ha-Ras, Rap1B, and RalA. In Rac1, TpeL and TcdB share the same acceptor amino acid for glycosylation, Thr-35. In Vero cells treated with TpeL1-525 in the presence of SLO, glycosylation leads to a translocation of the majority of Rac1 and Ha-Ras to the membrane. We demonstrate for first time that TpeL uses both UDP-GlcNAc and UDP-Glc as donor cosubstrates and modifies the Rac1 and Ras subfamily by glycosylation to mediate its cytotoxic effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Clostridium perfringens
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Proteínas ras
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Citotoxinas
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article