SOLUTION STRUCTURE MODEL OF RESIDUES 1-28 OF THE AMYLOID BETA -PEPTIDE WHEN BOUND TO MICELLES

The major protein constituent of amyloid deposits in Alzheimer's disease is the β-peptide, which in solution can fold as a random coil, monomeric α-helix, or oligomeric β-sheet structure, the latter structure being toxic and eventually precipitating as amyloid. In this report, using circular dichroism and nuclear magnetic resonance spectroscopic techniques, we demonstrate that in micelle solution the α-helical structure is the predominate structural motif and that its stability is highly dependent on the pH and the surface charge of the micelle. A peptide fragment comprised of residues 1−28 of the β-peptide [β-(1−28)], which occupies the presumed extracellular domain of the amyloid precursor protein and the negatively charged sodium dodecyl sulfate (SDS), the positively charged dodecyltrimethylammonium chloride (DTAC), and the zwitterionic, neutral dodecylphosphocholine (DPC), was utilized. In SDS and DPC, nuclear Overhauser enhancement spectroscopy and the αH chemical shifts showed that at pH 2−3 there a...