The Role of Lipid Environment on Peptide Structure and Folding

Abstract

Membrane proteins are an important class of proteins that are difficult to characterize structurally and functionally. In order to gain a better understanding of the forces that govern membrane protein folding and structure, a series of simple leucine-alanine peptides ranging from 12 to 18 residues were designed. The peptides were anchored by two lysine residues at each end and spontaneously inserted into negatively charged lipid bilayers. The effects of peptide length, lipid length, bilayer/micelle composition and the presence of structure breaking residues glycine and proline on the uniformity of helical structure were evaluated. An increase in the intensities of the amide III and S bands in deep-UV resonance Raman spectra indicated loss of helical structure. Differences in peptide hydration were monitored using tryptophan fluorescence. Loss of helical structure was observed in cases of negative hydrophobic mismatch, increased peptide hydration and upon introduction helix breaking residues. No loss of helical structure was observed in cases of positive hydrophobic mismatch while the shortest peptide adopted beta-sheet structure in instances of negative hydrophobic mismatch. Greater hydration of the peptide, which occurred in surfactant/lipid micelles, magnified the helix breaking- effects of glycine and proline. These studies highlight the potential importance of the lipid environment itself on membrane protein structure.