Abstract :
[en] The involvement of membrane-bound peptides and the influence of protein conformations in several
neurodegenerative diseases lead us to analyze the interactions of model peptides with artificial membranes.
Two model peptides were selected. The first one, an alanine-rich peptide, K3A18K3, was shown to be in
R-helix structures in TFE, a membrane environment-mimicking solvent, while it was mostly -sheeted in
aqueous buffer as revealed by infrared spectroscopy. The other, alamethicin, a natural peptide, was in a stable
R-helix structure. To determine the role of the peptide conformation on the nature of its interactions with
lipids, we compared the structure and topology of the conformational-labile peptide K3A18K3 and of the R-helix
rigid alamethicin in both aqueous and phospholipid environments (Langmuir monolayers and multilamellar
vesicles). K3A18K3 at the air-water interface showed a pressure-dependent orientation of its -sheets, while
the R-helix axis of alamethicin was always parallel to the interface, as probed by polarization modulation
infrared reflection absorption spectroscopy. The -sheeted K3A18K3 peptide was uniformly distributed into
DPPC condensed domains, while the helical-alamethicin insertion distorted the DPPC condensed domains,
as evidenced by Brewster angle microscopy imaging of the air/interface. The -sheeted K3A18K3 interacted
with DMPC multilamellar vesicles via hydrophilic interactions with polar heads and the helical-alamethicin
via hydrophobic interactions with alkyl chains, as shown by infrared spectroscopy and solid state NMR. Our
findings are consistent with the prevailing assumption that the conformation of the peptide predetermines the
mode of interaction with lipids. More precisely, helical peptides tend to be inserted via hydrophobic interactions
within the hydrophobic region of membranes, while -sheeted peptides are predisposed to interact with polar
groups and stay at the surface of lipid layer
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