Positioning of the Alzheimer Abeta(1-40) Peptide in SDS Micelles Using NMR and Paramagnetic Probes

J Biomol NMR. 2007 Sep;39(1):63-72. doi: 10.1007/s10858-007-9176-4. Epub 2007 Jul 27.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemistry*
  • Carbon Isotopes
  • Diffusion
  • Magnetics / instrumentation*
  • Micelles*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Peptide Fragments / chemistry*
  • Peptides / chemistry*
  • Protons
  • Sodium Dodecyl Sulfate / chemistry*

Substances

  • Amyloid beta-Peptides
  • Carbon Isotopes
  • Micelles
  • Peptide Fragments
  • Peptides
  • Protons
  • amyloid beta-protein (1-40)
  • Sodium Dodecyl Sulfate