Review: model peptides and the physicochemical approach to beta-amyloids.
beta-Amyloid peptides are the main protein components of neuritic plaques and may be important in the pathogenesis of Alzheimer's Disease. The determination of the structure of beta-amyloid fibrils poses a challenge because of the limited solubility of beta-amyloid peptides and the noncrystalline nature of fibrils formed from these peptides. In this paper, we describe several physicochemical approaches which have been used to examine fibrils and the fibrillogenesis of peptide models of beta-amyloid. Recent advances in solid state NMR, such as the DRAWS pulse sequence, have made this approach a particularly attractive one for peptides such as beta-amyloid, which are not yet amenable to high-resolution solution phase NMR and crystallography. The application of solid state NMR techniques has yielded information on a model peptide comprising residues 10-35 of human beta-amyloid and indicates that in fibrils, this peptide assumes a parallel beta-strand conformation, with all residues in exact register. In addition, we discuss the use of block copolymers of Abeta peptides and polyethylene glycol as probes for the pathways of fibrillogenesis. These methods can be combined with other new methods, such as high-resolution synchrotron X-ray diffraction and small angle neutron and X-ray scattering, to yield structural data of relevance not only to disease, but to the broader question of protein folding and self-assembly.
Department of Chemistry, The University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois, 60637-1403, USA.
D G
DG
Lynn
S C
SC
Meredith
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D001483:Base Sequence; D002627:Chemistry, Physical / Q000379:methods; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D010455:Peptides