Amphipathic α-helices in proteins: results from analysis of protein structures

Abstract

Amphipathic α-helices play a crucial role in mediating the interaction of peptides and proteins with membranes. We have analyzed protein structures for the occurrence of 18-residue amphipathic helices. We find several of these α-helices having average hydrophobic moments and average hydrophobicities that would favor their interaction with membranes. We have analyzed the distribution of net charge, helix length, normalized frequency of occurrence, and propensities of the 20 amino acids in the delineated 18-residue helices. We have observed distinct differences in the frequencies of occurrence of polar and hydrophobic amino acids at positions 1-18 in amphipathic and nonamphipathic helices. There are also differences in propensities of the 20 amino acids to occur at positions 1-18 of amphipathic and nonamphipathic helices. Synthetic peptides corresponding to some of these surface-seeking helices do possess antibacterial and/or hemolytic activities. Knowledge of the distribution of charges in 18-residue surface-seeking amphipathic α-helices, as well as propensity of occurrence of amino acids at various positions, would be useful inputs in the de novo design of amphipathic peptides.