Positioning of the Alzheimer Aβ(1–40) peptide in SDS micelles using NMR and paramagnetic probes

Abstract

NMR spectroscopy combined with paramagnetic relaxation agents was used to study the positioning of the 40-residue Alzheimer Amyloid beta-peptide Abeta(1-40) in SDS micelles. 5-Doxyl stearic acid incorporated into the micelle or Mn(2+) ions in the aqueous solvent were used to determine the position of the peptide relative to the micelle geometry. In SDS solvent, the two alpha-helices induced in Abeta(1-40), comprising residues 15-24, and 29-35, respectively, are surrounded by flexible unstructured regions. NMR signals from these unstructured regions are strongly attenuated in the presence of Mn(2+) showing that these regions are positioned mostly outside the micelle. The central helix (residues 15-24) is significantly affected by 5-doxyl stearic acid however somewhat less for residues 16, 20, 22 and 23. This alpha-helix therefore resides in the SDS headgroup region with the face with residues 16, 20, 22 and 23 directed away from the hydrophobic interior of the micelle. The C-terminal helix is protected both from 5-doxyl stearic acid and Mn(2+), and should be buried in the hydrophobic interior of the micelle. The SDS micelles were characterized by diffusion and (15)N-relaxation measurements. Comparison of experimentally determined translational diffusion coefficients for SDS and Abeta(1-40) show that the size of SDS micelle is not significantly changed by interaction with Abeta(1-40).