Three-dimensional structures insulin receptor

The abundant IGF-I (somatomedin C), a 70-residue single-chain basic peptide with a sequence and three-dimensional structure homologous to that of proinsu-lin,206.207 jg considered a major mediator of the action of fhe pifuitary growth hormone (GH, somatotropin). Studies in cell culture suggest that GH may induce differentiation of cells, and that IGF-I may then cause a rapid proliferation of the newly differentiated cells. The homologous 67-residue IGF-II may have a similar function in fetal development. TTie cell surface receptor for IGF-I is similar to the insulin receptor, but IGF-II receptor is structurally different. It is a monomeric 250-kDa protein and although it is a substrate for a fyrosine kinase, it has no kinase activity of its... 

Species variations in primary stmctnre are also important in medicine, as illustrated by the comparison of human, beef, and pork insulin. Insulin is one of the hormones that are highly conserved between species, with very few amino acid substitutions and none in the regions that affect activity. Insulin is a polypeptide hormone of 51 amino acids that is composed of two polypeptide chains (Fig. 6.13). It is synthesized as a single polypeptide chain, but is cleaved in three places before secretion to form the C peptide and the active insulin molecule containing the A and B chains. The folding of the A and B chains into the correct three-dimensional structure is promoted by the presence of one intrachain and two interchain disulfide bonds formed by cysteine residues. The invariant residues consist of the cysteine residues engaged in disulfide bonds and the residues that form the surface of the insulin molecule that binds to the insulin receptor. The amino acid substitutions in bovine and porcine insulin (shown in blue in Fig. 6.13.) are not in amino acids that affect its activity. Consequently, bovine and pork insulin were used for many years for the treatment of diabetes mellitus. However, even with only a few different amino acids, some patients developed an immune response to these insulins. 

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