Secondary structures of lipid-associating peptides: a Fourier transform infrared study

Four peptides from 20 to 28 residues in length were studied by Fourier transform infrared (FTIR) spectroscopy in solution and in complexes with dimyristoylphosphatidylcholine (DMPC). The four peptides included the 20-residue lipid-associating peptide, LAP-20, which was predicted to form an amphipathic helical structure in the presence of lipids, and three other peptides whose sequences had less amphipathic helix-forming properties. The complexes were shown by electron microscopy to be discoidal in shape with mean diameters of 21-27 nm. At the concentrations used for IR, the peptides appeared to form oligomers consisting of intermolecular beta-sheets. In the presence of lipids, the amount of beta-structure decreased; however, amounts of beta-structure were still approximately equal to amounts of alpha-helix. The IR results for LAP-20 contradicted previous circular dichroism results that predicted 50%-90% alpha-helix in DMPC complexes. Convex constraint analysis (CCA) deconvolution of the circular dicroism (CD) spectrum to estimate secondary structures predicted amounts of helix similar to those predicted by IR, but there was still substantial disagreement between IR and CD estimates of other secondary structures. For LAP-20 in complexes, CD predicted random structure. Possible physiological consequences of partial disordering of peptide structures are discussed.