2.8 Insulin and its Genes

We now may examine the amino acid sequence of insulin and how its gene is organized. Insulin is a small protein made up of two peptide chains held together by disulfide bonds between cysteine residues. The A chain has 21 amino acids and the B chain 30. The amino acid sequence was determined by Sanger in 1955.

Figure 14. The structure of insulins from various sources

Insulin is produced only in the beta cells of the pancreas. Of course, the gene for insulin is in all cells, but insulin is not produced in other tissues because of special control regions that lie in front of the gene and prevent it from being expressed. Proinsulin is the precursor of insulin and contains an extra peptide chain (the C chain). The C chain that links chains A and B allows the entire molecule to be synthesized in the b-cell as one protein.The C chain is split out after proinsulin is made to give the mature insulin structure of 51 amino acids with a molecular weight of 5,700 .

Insulin is actually produced in the b-cell as preproinsulin with an extra 24 amino acids which serves to guide the new protein to vesicles where it is stored. This "signal sequence" is removed shortly after protein synthesis begins.

Figure 15. Processing of insulin precursors to give mature insulin

Insulin is a member of a large family of related proteins and over 80 of these have been sequenced. Even insects have insulin-like proteins. The disulfide bonds are conserved, and the molecules form three helices in their native form. The three-dimensional shape of the insulin molecule is shown in the figure. Other animal insulins have almost identical amino acid sequences to that of human insulin, which means that we may sometimes use them in place of human insulin.

Pork insulin has only one amino acid change; in chain B at position 30, alanine is found in place of threonine.

Beef insulin has two additional changes; in chain A at position 8, alanine is found in place of threonine and at position 10, valine is found in place of isoleucine.