The structure of a protein hormone, insulin

Abstract

Hormones are chemical substances involved in the regulation and integration of metabolic processes. For the first time, the three-dimensional structure of a protein hormone, insulin, has been worked out by X-ray crystallographio analysis using isomorphous replacement and anomalous scattering methods. The basic repeating unit in the crystals studied is an insulin hexamer. The three dimers in the hoxamer are related to one another by a crystallographio threefold axis. The two molecules in each dimer are related to each other by a local twofold axis. In the insulin molecule the two polypeptide chains, the A and the B chains, are held together by two disulphide bridges, and hydrophobic and polar side chain interactions. The dimer structure is stabilized by hydrophobic interactions and interchain hydrogen bonds. The stabilization of the hexamer is achieved by predominantly non-polar interactions between adjacent dimers and the co-ordination of the molecules to the two zinc ions on the threefold axis. Finally, the analysis provides some interesting insights into the relationship between the structure and the biological role of insulin.