Effects of thallium (I) on the structure and functions of mammalian ribosomes

Abstract

(1) The administration of lethal doses of TINO 3 to mice resulted in a reduced incorporation of amino acids into protein in vivo and a disaggregation of liver polyribosomes. Preparations of liver ribosomes showed a decreased activity in both endogenous and poly(U)-directed amino acid incorporation, suggesting that some particles had been persistently damaged. (2) At low concentrations Tl + was uniquely effective in protecting isolated mammalian ribosomes against irreversible inactivation by K + deficiency. However, already at moderately increased concentrations the protective effect disappeared and was replaced by a progressive destabilization, to which the 60S subunits were particularly susceptible. Comparable results could be obtained with K +, but only at concentrations that were 4.5–20 times higher. (3) Tl + could replace K + in some partial ribosomal functions (the poly(U)-directed binding of phenylalanyl-tRNA and the puromycin-induced release of nascent polypeptides), but at 40–50 m M Tl + the instability of the 60S subunit became a limiting factor. By contrast, Tl + was entirely inactive in both poly(U)-directed and endogenous amino acid incorporation. In the presence of K +, Tl + was inhibitory even at low concentrations. The inhibition was not markedly counteracted by K + or mereaptoethanol. (4) The inhibition of amino acid incorporation by Tl + is primarily ascribed to the strong interaction of Tl + with normally K +-occupied ribosomal sites. The tendency of Tl + to react with ‘soft’, b-type electron donors, e.g. thiols, seems to be of minor importance. It is hypothesized that the heavy and strongly binding Tl + ions may block some reaction in the translocation cycle which depends on recurrent K + translocations.