Insulin receptors and insulin receptor antibodies: structure-function relationships

The insulin receptor has been purified by affinity chromatography and studied by affinity-labelling techniques. It appears to be a disulphide-linked heterotetramer, (alpha beta)2, composed of two copies of a 135,000 Mr subunit (alpha), and two copies of a 90,000 Mr subunit (beta). Beta is readily proteolysed to generate a 45,000 Mr fragment (beta 1). Alpha, beta and beta 1 all contain sialic acid and are, therefore, probably all exposed on the external surface of the membrane. Although alpha is predominantly labelled in affinity-labelling studies, beta and beta 1 can also be labelled. Therefore, alpha, beta and beta 1 are all in proximity to the insulin-binding site and may contain part of the binding site. Antibodies have been prepared against the intact, purified receptor and against the isolated alpha subunit. Both antibodies directly interact with the insulin receptor as indicated by their ability to immunoprecipitate the receptor. Neither antibody, however, directly competes with insulin binding. Therefore, they are probably directed against regions of the receptor distinct from the insulin-binding site. In spite of this, these antibodies have a wide range of insulin-like activities.