Stabilization of alpha helices by ion pairs

Abstract

A survey of 50 protein structures (47 globular and 3 fibrous) indicates that intrahelical ion pairs between oppositely charged residues (Glu^-, Asp^-/Lys⁺, Arg⁺) 3 or 4 residues apart along the helix may have a stabilizing effect on alpha helices exposed to solvent. It is found that the i, i ± 3/4 types of ion pairs are the most predominant, and their observed frequencies are significantly greater than their expected frequencies. Such a preference is not seen for the like-charged pairs which served as a control. It was found that the normalized frequencies of these ion pairs increased with the helix length. An analysis of the distances between the charged groups in ion pairs suggests that only about 20% of the ion pairs are stabilized by hydrogen bonding (salt bridged), about 40% by electrostatic interactions, and the remaining may be stabilized by solvation: forming water bridges or plumes of water molecules around the charged groups. The fibrous proteins, which have a proportionately larger solvent exposed area than the globular proteins, have a higher density of intrahelical or secondary structural ion pairs. They are distinguished from the globular proteins which contain fewer ion pairs/charged residues because of their smaller solvent exposed area. The results indicate that the ion pairs may have a stabilizing effect on alpha helices exposed to solvent.