The roles of tryptophan residues in the structure, function, and folding of the gramicidin transmembrane ion channel.

Abstract

Gramicidin is a polypeptide antibiotic which forms ion channels in phospholipid membranes. Four out if its 15 residues are tryptophans, and hence it is not surprising that they play major role in its structure, function and folding. Gramicidin adopts two major types of ion-conducting structures that have very different conformational and functional proper­ties; these two structures are known as the “pore” and the “channel” forms. The pore consists of two intertwined polypeptide strands which form an antiparallel double helix that spans the membrane, while the channel is formed by two single helices that abut each other in the centre of the membrane forming a helical dimer. However, in addition to having entirely different backbone folds, the pore and the channel differ distinctly in the conformation and orientation of their tryptophan side chains: in the pore, all tryptophans lie essentially parallel to the helix axis, creating a smooth, uniform cylindrical shape to the molecule, while in the channel the tryptophan side chains lie nearly perpendicular to the helical axis. Because the tryptophans are located near the C-termini of the two monomers, this means the channel has a head-to-head double conical shape.