Effect of modeccin on the steps of peptide-chain elongation.
Modeccin inhibits polypeptide-chain elongation catalysed by Artemia salina (brine shrimp) ribosomes by inactivating the 60 S ribosomal subunit. Among the individual steps of elongation, peptide-bond formation, catalysed by 60 S peptidyltransferase, is unaffected by the toxin, whereas the binding of EF 2 (elongation factor 2) to ribosomes is strongly inhibited. Modeccin does not affect the poly(U)-dependent non-enzymic binding of either deacylated tRNAPhe or phenylalanyl-tRNA to ribosomes. The inhibitory effect of modeccin on the EF 1 (elongation factor 1)-dependent binding of phenylalanyl-tRNA is discussed, since it is decreased by tRNAPhe, which stimulates the binding reaction. The analysis of the distribution of ribosome-bound radioactivity during protein synthesis shows that modeccin consistently inhibits the radioactivity bound as long-chain peptides, but depending on the experimental conditions, can leave unchanged or even greatly stimulates the radioactivity bound as phenylalanyl-tRNA and/or short-chain peptides. It is concluded that, during the complete elongation cycle, modeccin does not affect the binding of the first aminoacyl-tRNA to ribosomes, but inhibits some step in the subsequent repetitive activity of either EF 1 or EF 2. The results obtained indicate that the mechanism of action of modeccin is very similar to that of ricin and related plant toxins such as abrin and crotin.
D000818:Animals; D001156:Artemia; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology*; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects*; D010445:Peptide Elongation Factors / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D011072:Poly U / Q000494:pharmacology; D014176:Protein Biosynthesis; D011691:Puromycin / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology*
D037102:Lectins; D010445:Peptide Elongation Factors; D012346:RNA, Transfer, Amino Acyl; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D011072:Poly U; D010649:Phenylalanine; D011691:Puromycin; C016004:modeccin
J Biol Chem. 1951 Nov;193(1):265-75
14907713
Biochem J. 1978 Aug 15;174(2):491-6
708401
Biochem Biophys Res Commun. 1977 Dec 21;79(4):1176-83
603653
FEBS Lett. 1977 Dec 20;85(1):65-7
598521
Eur J Biochem. 1976 Dec;71(1):271-9
1009951
Biochemistry. 1976 Oct 5;15(20):4364-9
974064
Proc Natl Acad Sci U S A. 1974 Jul;71(7):2693-7
4527774
Biochem J. 1975 Jun;148(3):447-51
173282
Biochim Biophys Acta. 1972 May 9;266(2):543-7
4338881
FEBS Lett. 1972 Jun 1;23(1):95-9
4343622
Biochemistry. 1974 Jan 1;13(1):196-204
4202710
J Biol Chem. 1974 May 25;249(10):3061-7
4830236
Biochem J. 1973 Nov;136(3):677-83
4780693
J Biol Chem. 1973 Apr 25;248(8):2853-7
4697394
Proc Natl Acad Sci U S A. 1971 Dec;68(12):3059-63
4943553
Biochem Biophys Res Commun. 1966 Oct 20;25(2):233-8
5339543
Eur J Biochem. 1976 May 1;64(2):437-43
1278169
Eur J Biochem. 1976 Apr 15;64(1):69-75
1278160
Biochem J. 1976 Apr 15;156(1):7-13
942404
Eur J Biochem. 1975 Jun;54(2):499-503
1175595
Dev Biol. 1968 Feb;17(2):143-64
5637102