| Abstract: | Theself-assembly of the soluble peptide Aβ into Alzheimer's disease amyloid is believed to involve a conformational change. Hence the solution conformation of Aβ is of significant interest. In contrast to studies in other solvents, in water Aβ is collapsed into a compact series of loops, strands, and turns and has no α-helical or β-sheet structure. Conformational stabilization is primarily attributed to van der Waals and electrostatic forces. A large conspicuous uninterrupted hydrophobic patch covers 25% of the surface. The compact coil structure appears meta-stable, and because fibrillization leads to formation of intermolecular β-sheet secondary structure, a global conformational rearrangement is highly likely. A molecular hypothesis for amyloidosis includes at least two primary driving forces, changes in solvation thermodynamics during formation of amyloid deposits and relief of internal conformational stress within the soluble precursor during formation of lower-energy amyloid fibrils. |
