Inhibition by ricin of protein synthesis in vitro. Ribosomes as the target of the toxin.
1. Ricin (a toxic protein from the seeds of Ricinus communis) is a powerful inhibitor of the poly(U)-directed incorporation of phenylalanine into polypeptides catalysed by isolated rat liver ribosomes and elongation factors 1 and 2 (EF 1 and EF 2). The inhibition can be largely overcome by increasing the concentration of ribosomes. 2. The toxin does not affect the binding of phenylalanyl-tRNA to ribosomes catalysed by EF 1, nor does it inhibit the puromycin reaction used as a test for peptide-bond formation catalysed by ribosomes. 3. Ricin inhibits the ribosome-linked GTP hydrolysis catalysed by EF 2. 4. Ribosomes treated with ricin and washed through sucrose gradients containing 0.6m-NH(4)Cl are functionally inactive in those assay systems that are sensitive to the presence of added toxin. 5. It is suggested that ricin brings about an irreversible modification of ribosomes which impairs their ability to interact with EF 2. Since ricin inhibits at a molar concentration much lower than that of ribosomes it probably acts catalytically. No added cofactor is necessary for the inhibitory action of the toxin.
D000818:Animals; D002499:Centrifugation, Density Gradient; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010445:Peptide Elongation Factors; D010649:Phenylalanine; D037121:Plant Lectins; D010947:Plants, Toxic; D014176:Protein Biosynthesis; D011691:Puromycin; D012343:RNA, Transfer / Q000378:metabolism; D051381:Rats; D012270:Ribosomes / Q000187:drug effects*; D012276:Ricin / Q000494:pharmacology; D012278:Ricinus; D014118:Toxins, Biological / Q000494:pharmacology*; D014316:Tritium
D010445:Peptide Elongation Factors; D037121:Plant Lectins; D014118:Toxins, Biological; D014316:Tritium; D010649:Phenylalanine; D011691:Puromycin; D006160:Guanosine Triphosphate; D012276:Ricin; D012343:RNA, Transfer