Structure, orientation and affinity for interfaces and lipids of ideally amphipathic lytic LiKj(i=2j) peptides.
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.
Castano
S
S
Centre de Recherche Paul Pascal, CNRS, Avenue A. Schweitzer, 33600, Pessac, France.
Desbat
B
B
Laguerre
M
M
Dufourcq
J
J
D000388:Air; D000595:Amino Acid Sequence; D003619:Dansyl Compounds / Q000737:chemistry; D006460:Hemolysin Proteins / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011312:Pressure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry
D003619:Dansyl Compounds; D006460:Hemolysin Proteins; D008055:Lipids; D010455:Peptides; D014867:Water