Positioning of the Alzheimer A beta(1-40) peptide in SDS micelles using NMR and paramagnetic probes

NMR spectroscopy combined with paramagnetic relaxation agents was used to study the positioning of the 40-residue Alzheimer Amyloid beta-peptide A beta(1-40) in SDS micelles. 5-Doxyl stearic acid incorporated into the micelle or Mn2+ ions in the aqueous solvent were used to determine the position of the peptide relative to the micelle geometry. In SDS solvent, the two a-helices induced in A beta(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 Mn2+ 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 a-helix therefore resides in the SDS head-group 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 Mn2+, and should be buried in the hydrophobic interior of the micelle. The SDS micelles were characterized by diffusion and N-15-relaxation measurements. Comparison of experimentally determined translational diffusion coefficients for SDS and A beta(1-40) show that the size of SDS micelle is not significantly changed by interaction with A beta(1-40).