Structural and crystallographic observations on hagfish insulin

Abstract

INSULIN is a well defined globular protein made up of two small peptide chains linked together through disulphide bonds^1,2. It contains an unusually high proportion of hydrophobic residues and thus tends to readily self-associate^3,4. In many species the hormone forms dimers in solution and, in the presence of Zn^2,4ions, hexamers^4,5. Recently, Hodgkin and coworkers^6,7 have determined the crystal structure of the rhombohedral form of porcine Zn-insulin at 1.9 Å resolution^6,7. Two molecules of insulin occur in the asymmetric unit, related through an approximate twofold axis to form a nearly symmetrical dimer. Three such dimers in turn associate through coordination of histidine residues B10 with two zinc ions to form a nearly spherical hexamer. In spite of the availability of the amino acid sequences of a wide variety of vertebrate insulins^2,8, however, comparative studies on the detailed structure and modes of association of vertebrate insulins have been lacking.