title: The mode of action of Shiga toxin on peptide elongation of eukaryotic protein synthesis.
abstract: The effect of Shiga toxin, from Shigella dysenteriae 1, on the component reactions of peptide elongation were investigated. Enzymic binding of [3H]phenylalanine-tRNA to reticulocyte ribosomes was inhibited by 50% at 7 nM toxin. Elongation factor 1 (eEF-1)-dependent GTPase activity was also inhibited. Both reactions were not restored by addition of excess eEF-1 protein. In contrast, toxin concentrations of 200 nM were required to inhibit by 50% the elongation factor 2 (eEF-2)-dependent translocation of aminoacyl-tRNA on ribosomes. Addition of excess eEF-2 restored translocation activity. The eEF-2-dependent GTPase activity was unaffected at toxin concentrations below 100 nM, and Shiga-toxin concentrations of up to 1,000 nM did not affect either GTP.eEF-2.ribosome complex-formation or peptidyltransferase activity. Thus Shiga toxin closely resembles alpha-sarcin in action, both being primary inhibitors of eEF-1-dependent reactions. In contrast, the 60 S ribosome inactivators ricin and phytolaccin are primary inhibitors of eEF-2-dependent reactions of peptide elongation.
authors: Department of Microbiology and Immunology, Albany Medical College, NY 12208.
authors: T G
authors: TG
authors: Obrig
authors: T P
authors: TP
authors: Moran
authors: J E
authors: JE
authors: Brown
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D010441:Peptide Chain Elongation, Translational; D010458:Peptidyl Transferases / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012270:Ribosomes; D022603:Shiga Toxins; D014178:Translocation, Genetic
chemical_list: D001427:Bacterial Toxins; D012346:RNA, Transfer, Amino Acyl; D022603:Shiga Toxins; D010458:Peptidyl Transferases; D020558:GTP Phosphohydrolases