Cation-pi interactions studied in a model coiled-coil peptide.

Abstract

Cation-pi interactions between aromatic amino acids and the positively charged residues lysine and arginine have been proposed to play an important role in stabilizing protein structure. We have used a peptide that adopts a coiled coil structure as a model system to evaluate the energetic contribution of cation-pi interactions to protein folding. Peptides were designed in which phenylalanine, tyrosine, and tryptophan were placed at a solvent-exposed position of the helix, one turn removed from an arginine residue that could provide a favorable cation-pi interaction. Only the arginine-phenylalanine pairing provided significant stabilization of the peptide structure and it appears that hydrophobic packing, rather than the cation-pi effect, is more likely to be responsible for the stability of this peptide. We conclude that any stabilizing effect of cation-pi interactions in these peptides is much smaller than that predicted from computational studies.