Conformational studies and pore-forming properties of an α-aminoisobutyric acid analogue of gramicidin B

Abstract

Structure-function relation of a designed α-aminoisobutyric acid (Aib) analogue of gramicidin B (GBA), a model for helical protein structures, is examined by CD and patch-clamp experiments. This 16-residue peptide adopts stable helical structures in organic and aqueous solvent sytems, and phospholipid vesicles. The content of the helical structure in egg yolk phosphatidylcholine vesicles increases with the increase of lipid-to-peptide molar ratio, suggesting adsorption and incorporation processes. A possible helix–helix interaction is observable at low peptide-to-lipid molar ratios. The role of Trp side-chains for the rather high affinity of this peptide for membrane surfaces is stressed. Though shorter than the average thickness of phospholipid bilayers, GBA forms voltage-dependent multi-state ion-conducting pores in diphytanoyl phosphatidylcholine bilayers formed at the tip of micropipettes, at relatively low concentrations. A range of GBA conductances is comparable to membrane protein channels. GBA pores show a variety of conducting behaviours as well as rectifying properties.