Conformational effects of cations and pH on human growth hormone in solution.

Abstract

Human GH (hGH) binding to membrane receptors is uniquely enhanced by 10 mM Ca++ and Mg++ or 150 tnM Na+ and K+. This study has used polarization of fluorescence (P) and circular dichroism (CD) to identify cation-dependent conformational alterations in hGH. CD indicated that the secondary structure of hGH consisted of 52% a-helix structure, 23% β-structure, and 25% disordered structure at pH 7.5. Increases in pH caused a small increase in a-helix structure to 55% at pH 10.5 with little change in β- structure. Decreases in pH from 7.5 resulted in decreases in ahelix and β-structure to 44% and 8%, respectively, at pH 4.1. Relatively large decreases in ordered structure occurred between pH 6 and 4. This corresponded to the pH optimum of hGH binding to membranes at pH 5.5. Cation-specific changes in structure were observed with increases in cation concentration generally associated with increases in ordered structure, i.e. α-helix and/or β-structure. The cation concentration range in which changes in structure...