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Fusogenic Alzheimer's peptide fragment Aβ (29–42) in interaction with lipid bilayers: Secondary structure, dynamics, and specific interaction with phosphatidyl ethanolamine polar heads as revealed by solid‐state NMR
Author(s) -
Ravault Stéphanie,
Soubias Olivier,
Saurel Olivier,
Thomas Annick,
Brasseur Robert,
Milon Alain
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.041291405
Subject(s) - popc , chemistry , peptide , lipid bilayer , crystallography , deuterium nmr , bilayer , phospholipid , stereochemistry , solid state nuclear magnetic resonance , nuclear magnetic resonance spectroscopy , membrane , nuclear magnetic resonance , biochemistry , physics
The interaction of the native Alzheimer's peptide C‐terminal fragment Aβ (29–42), and two mutants (G33A and G37A) with neutral lipid bilayers made of POPC and POPE in a 9:1 molar ratio was investigated by solid‐state NMR. This fragment and the lipid composition were selected because they represent the minimum requirement for the fusogenic activity of the Alzheimer's peptide. The chemical shifts of alanine methyl isotropic carbon were determined by MAS NMR, and they clearly demonstrated that the major form of the peptide equilibrated in membrane is not in a helical conformation. 2 H NMR, performed with acyl chain deuterated POPC, demonstrated that there is no perturbation of the acyl chain's dynamics and of the lipid phase transition temperature. 2 H NMR, performed with alanine methyl‐deuterated peptide demonstrated that the peptide itself has a limited mobility below and above the lipid phase transition temperature (molecular order parameter equal to 0.94). MAS 31 P NMR revealed a specific interaction with POPE polar head as seen by the enhancement of POPE phosphorus nuclei T 2 relaxation. All these results are in favor of a β‐sheet oligomeric association of the peptide at the bilayer interface, preferentially recruiting phosphatidyl ethanolamine polar heads.