Mapping of the residues responsible for the negative cooperativity of the receptor-binding region of insulin.
Insulin binding to its receptor leads to negatively cooperative interactions among the receptor sites. Studies with 29 insulin analogues (animal insulins and proinsulin, insulin-like growth factor and chemically modified insulins) which vary 1,000-fold in their affinity for the receptor and in their biological potency, suggest that a discrete invariable region on the surface of the insulin monomer is responsible for including the negative cooperativity. This domain comprises some of the eight carboxy-terminal residues of the B-chain and the A21 asparagine. Burying of this 'cooperative site' in the dimerisation of insulin leads to a loss of negative cooperativity. A revised mapping of the insulin molecule is proposed, featuring distinct bioactive and cooperative sites.
D000495:Allosteric Site; D000818:Animals; D006728:Hormones / Q000378:metabolism; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D011972:Receptor, Insulin / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship
D006728:Hormones; D007328:Insulin; D046911:Macromolecular Substances; D011972:Receptor, Insulin