Charge distributions and amphipathicity of receptor-binding alpha-helices.

Contacts between ligands and cell-surface receptors result in cellular activation. Defining principles which govern these important interactions are of interest and might facilitate pharmacologic intervention. We examined receptor-binding alpha-helical segments of polypeptide hormones and globular proteins for distinguishing amino acid content and distributions. There was a slight excess of basic residues in both sets of alpha-helices compared with a panel of control helices. Helical concentrations of charged residues were quantitated using the hydrophobic moment algorithm, adapted to obtain the vector sum of side chain charges. By this analysis we detected increased concentrations of the set of basic residues (arginine, lysine and histidine) on one side of the receptor-binding alpha-helices of the polypeptide hormones, and to a lesser extent the protein ligands. Comparable data were obtained for "lytic" venom peptides and calmodulin-regulated kinase segments. There was an even greater correlation between receptor-associating alpha-helical segments and large hydrophobic moments. Receptor-binding helical segments of polypeptide hormones, and to a lesser extent those of protein ligands, often are basic and amphipathic.