Protection and Rescue of Ribosomes from the Action of Ricin A Chain

Daniel B. Cawley1, Mary L. Hedblom, L. L. Houston

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The effect of ricin A chain on the translation of synthetic and natural mRNA by mammalian and wheat germ ribosomes was studied. Both rat liver and wheat germ ribosomes were inactivated in the absence of soluble factors, nucleotides and energy-regenerating components; however, rat liver ribosomes were much more sensitive to ricin A chain than wheat germ ribosomes. A high concentration (16 mM) of Mg2+ reduced considerably the amount of inhibition of both rat liver and wheat germ ribosomes compared with that observed with 10 mM Mg2+. These results indicate that Mg2+ can partially restore activity of A chain treated ribosomes, perhaps as a result of an induced conformational change. At high Mg2+ concentrations, GTP was able to partially overcome A chain inhibition of protein synthesis. Although the com bination of EF-2 and GTP did not prevent the binding of [3H]NEM-labeled A chain to rat liver ribosomes, EF-2 and guanyl-5'-yl imidodiphosphate, a nonhydrolyzable GTP analogue which stabilizes the binding of EF-2 to ribosomes, did prevent binding of A chain. Increasing concentrations of yeast tRNA, in the absence of nucleotides and elongation factors, inhibited A chain binding to rat liver ribosomes and protected ribosomes from inactivation. Poly(uridylic acid) had no effect on binding. The protective effects of EF-2 and tRNA suggest that the binding site of the A chain and the site of the enzymatic lesion are the same and that ribosomes that contain EF-2 or tRNA are inaccessible to A chain and cannot be inactivated except during specific phases of protein synthesis.

Original languageEnglish (US)
Pages (from-to)2648-2654
Number of pages7
JournalBiochemistry
Volume18
Issue number12
DOIs
StatePublished - Jan 1 1979

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cawley1, D. B., Hedblom, M. L., & Houston, L. L. (1979). Protection and Rescue of Ribosomes from the Action of Ricin A Chain. Biochemistry, 18(12), 2648-2654. https://doi.org/10.1021/bi00579a034