Just I, Selzer J, Hofmann F, Green G A, Aktories K
Institut für Pharmakologie und Toxikologie der Universität Freiburg, Hermann-Herder-Strasse 5, D-79104 Freiburg, Germany.
J Biol Chem. 1996 Apr 26;271(17):10149-53. doi: 10.1074/jbc.271.17.10149.
The lethal toxin (LT) from Clostridium sordellii belongs to the family of large clostridial cytotoxins causing morphological alterations in cultured cell lines accompanied by destruction of the actin cytoskeleton. C. sordellii LT exhibits 90% homology to Clostridium difficile toxin B, which has been recently identified as a monoglucosyltransferase (Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., Mann, M., and Aktories, K. (1995) Nature 375, 500-503). We report here that LT too is a glucosyltransferase, which uses UDP-glucose as cosubstrate to modify low molecular mass GTPases. LT selectively modifies Rac and Ras, whereas the substrate specificity of toxin B is confined to the Rho subfamily proteins Rho, Rac, and Cdc42, which participate in the regulation of the actin cytoskeleton. In Rac, both toxin B and LT share the same acceptor amino acid, threonine 35. Glucosylation of Ras by LT results in inhibition of the epidermal growth factor-stimulated p42/p44 MAP-kinase signal pathway. LT is the first bacterial toxin to inactivate Ras in intact cells.
索氏梭菌的致死毒素（LT）属于大梭菌细胞毒素家族，可在培养的细胞系中引起形态学改变，并伴有肌动蛋白细胞骨架的破坏。索氏梭菌LT与艰难梭菌毒素B具有90%的同源性，后者最近被鉴定为一种单葡萄糖基转移酶（Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., Mann, M., and Aktories, K. (1995) Nature 375, 500 - 503）。我们在此报告，LT也是一种葡萄糖基转移酶，它以UDP-葡萄糖作为共底物来修饰低分子量GTP酶。LT选择性地修饰Rac和Ras，而毒素B的底物特异性仅限于参与肌动蛋白细胞骨架调节的Rho亚家族蛋白Rho、Rac和Cdc42。在Rac中，毒素B和LT共享相同的受体氨基酸，即苏氨酸35。LT对Ras的糖基化导致表皮生长因子刺激的p42/p44 MAP激酶信号通路受到抑制。LT是第一种能使完整细胞中的Ras失活的细菌毒素。
