Glucagon Conformation in Different Environments: Implications for Molecular Recognition

Abstract

Glucagon is a hormone which consists of a linear polypeptide chain of 29 amino acid residues and has a molecular weight of 3500. Early studies by circular dichroism and other physical-chemical techniques indicated a pronounced tendency of this polypeptide to adopt different spatial structures in different environments. For example, for monometric glucagon in aqueous solution a flexible “random coil” structure was indicated [1], and for self-aggregated glucagon in aqueous solution it was shown that it could adopt either an α-helical [2] or a β-sheet [3] secondary structure and that the species formed depended critically on the peptide concentration [4]. Furthermore, interactions with lipids and detergents were also found to induce changes of the glucagon conformation [5–7]. More recently, detailed descriptions based on many-parameter techniques were obtained for glucagon conformations in three different environments, i.e. in single crystals, in aqueous solution and in the lipid-water interphase near the surface of dodecylphosphocholine (DPC) micelles. The present paper describes some implications for studies of the mechanism of action of glucagon which result from comparison of these three molecular structures.