The nonclassical insulin binding of insulin receptors from rat liver is due to the presence of two interacting α-subunits in the receptor complex

The binding characteristics of the insulin receptor tetramer (α₂β₂) and dimer (αβ) were examined. Unlabelled insulin enhanced the dilution-induced dissociation only of the receptor tetramer-bound ¹²⁵I-insulin. Furthermore, when both the receptor forms had been preincubated with anti-receptor-antibodies (B9-antiserum), insulin binding only to the receptor tetramer but not to the dimer was inhibited. However, both oligomers are not immunologically distinct since more than 80% of the two forms were immunoprecipitated by the antiserum. These results suggest that both insulin and anti-receptor-antibodies induce cooperative interactions between the two linked α-subunits of the receptor tetramer leading to a decrease in insulin binding of this receptor form.