The Conformation of Insulin-Like Growth Factors: Relationships with Insulins

Abstract

SUMMARY The insulin-like growth factors and hystricomorph insulins have been modelled by interactive computer graphics on the assumption that their sequence homology to insulin implies that they will have a similar tertiary structure. These studies suggest that, although the insulin-related molecules can adopt the insulin fold, they are unlikely to form hexamers and if they form dimers they will be of reduced stability. The non-suppressibility of insulin-like growth factors by anti-insulin antibodies is explained in terms of differences of surface residues in the region A8–A10 and B1–B5. Receptor affinity of insulins and insulin-like growth factors for insulin receptors is explicable in terms of a receptor-binding site in the vicinity of B25 Phe on the insulin surface. An equivalent region around B25 Tyr of insulin-like growth factors may be responsible for their binding to type 1 receptors, although binding type 2 receptors must involve a different surface region not shared by insulin.