Structure, orientation and affinity for interfaces and lipids of ideally amphipathic lytic LiKj(i=2j) peptides

Biochim Biophys Acta. 1999 Jan 12;1416(1-2):176-94. doi: 10.1016/s0005-2736(98)00220-x.

Abstract

The behavior of lytic ideally amphipathic peptides of generic composition LiKj(i=2j) and named LKn, n=i+j, is investigated in situ by the monolayer technique combined with the recently developed polarization modulation IR spectroscopy (PMIRRAS). A change in the secondary structure occurs versus peptide length. Peptides longer than 12 residues fold into alpha-helices at interfaces as expected from their design, while enough shorter peptides, from 9 down to 5 residues, form intermolecular antiparallel beta-sheets. Analysis of experimental and calculated PMIRRAS spectra in the amide I and II regions show that peptides are flat oriented at the interfaces. Structures and orientation are preserved whatever the nature of the interface, air/water or DMPC monolayer, and the lateral pressure. Peptide partition constants, KaffPi, are estimated from isobar surface increases of DMPC monolayers. They strongly increase when Pi decreases from 30 mN/m to 8 mN/m and they vary with peptide length with an optimum for 12 residues. This non-monotonous dependence fits with data obtained in bilayers and follows the hemolytic activity of the peptides. Lipid perturbations due to peptide insertion essentially detected on the PO4- and CO bands indicate disorder of the lipid head groups. Lysis induced on membranes by such peptides is proposed to first result from their flat asymmetric insertion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air
  • Amino Acid Sequence
  • Dansyl Compounds / chemistry
  • Hemolysin Proteins / chemistry*
  • Lipids / chemistry*
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Pressure
  • Protein Conformation
  • Protein Structure, Secondary
  • Spectroscopy, Fourier Transform Infrared
  • Water / chemistry

Substances

  • Dansyl Compounds
  • Hemolysin Proteins
  • Lipids
  • Peptides
  • Water