RRC ID 18182
著者 Nagahama M, Ohkubo A, Oda M, Kobayashi K, Amimoto K, Miyamoto K, Sakurai J.
タイトル Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily proteins.
ジャーナル Infect Immun
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.
巻・号 79(2)
ページ 905-10
公開日 2011-2-1
DOI 10.1128/IAI.01019-10
PII IAI.01019-10
PMID 21098103
PMC PMC3028844
MeSH Animals Bacterial Toxins / metabolism* Chlorocebus aethiops Clostridium perfringens / genetics Clostridium perfringens / metabolism* Cytotoxins / metabolism* GTP Phosphohydrolases / metabolism Glycosylation Protein Binding Proto-Oncogene Proteins c-akt / metabolism* Recombinant Proteins Substrate Specificity Vero Cells ras Proteins / metabolism*
IF 3.201
引用数 34
WOS 分野 INFECTIOUS DISEASES IMMUNOLOGY
リソース情報
ヒト・動物細胞 Vero(RCB0001)