Effect of cupric ions on the initiation protein synthesis rate in the human endometrium

The effect of cupric ions on the initiation protein synthesis rate of the human endometrium was studied. Addition of copper to the complete ribosomal system decreased the binding of [3H]Met-tRNA(i) to the isolated ribosomes with a plateau at about 70% inhibition with concentrations higher than 150 microM. The initiation activity was GTP-dependent with a maximum at 2 mM. This activity was very rapid, requiring 5 min to complete the reaction. Incubation of isolated initiation factors with copper (300 microM) inhibited the formation of the ternary complex. When the complete system was reconstituted with salt-washed ribosomes after ternary complex formation, no significant change on the inhibition pattern was observed. Addition of initiation factors to 5-min preincubated salt-washed ribosomes with 300 microM copper, after the elimination of excess copper, induced only a 12% decrease on Met-tRNA(i) binding. This effect was not modified by the presence of Sparsomycin, an elongation inhibitor. It was concluded that copper interferes with the initiation process, probably at the ternary complex formation level.