The Alzheimer's peptide A beta adopts a collapsed coil structure in water

The self-assembly of the soluble peptide A beta into Alzheimer's disease am yloid is believed to involve a conformational change. Hence the solution co nformation of A beta is of significant interest, In contrast to studies in other solvents, in water A beta is collapsed into a compact series of loops , strands, and turns and has no alpha-helical or beta-sheet structure. Conf ormational stabilization is primarily attributed to van der Waals and elect rostatic forces. A large conspicuous uninterrupted hydrophobic patch covers similar to 25% of the surface. The compact coil structure appears meta-sta ble, and because fibrillization leads to formation of intermolecular beta-s heet secondary structure, a global conformational rearrangement is highly l ikely. A molecular hypothesis for amyloidosis includes at least two primary driving forces, changes in solvation thermodynamics during formation of am yloid deposits and relief of internal conformational stress within the solu ble precursor during formation of lower-energy amyloid fibrils. (C) 2000 Ac ademic Press.