Effect of modeccin on the steps of peptide-chain elongation

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Abstract
Modeccin inhibits polypeptide-chain elongation catalyzed by Artemia salina (brine shrimp) ribosomes by inactivating the 60S ribosomal subunit. Among the individual steps of elongation, peptide-bond formation, catalyzed by 60S 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 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. During the complete elongation cycle, modeccin does not affect the binding of the 1st aminoacyl-tRNA to ribosomes but inhibits some step in the subsequent repetitive activity of EF 1 or EF 2. The mechanism of action of modeccin is very similar to that of ricin and related plant toxins such as abrin and crotin.