期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：26
页码：16742-16747
DOI：10.1073/pnas.262663499
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We present a structural model for amyloid fibrils formed by the 40-residue {beta}-amyloid peptide associated with Alzheimer's disease (A{beta}1-40), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-{beta} structural motif established by x-ray fiber diffraction and satisfies constraints on A{beta}1-40 fibril dimensions and mass-per-length determined from electron microscopy. Approximately the first 10 residues of A{beta}1-40 are structurally disordered in the fibrils. Residues 12-24 and 30-40 adopt {beta}-strand conformations and form parallel {beta}-sheets through intermolecular hydrogen bonding. Residues 25-29 contain a bend of the peptide backbone that brings the two {beta}-sheets in contact through sidechain-sidechain interactions. A single cross-{beta} unit is then a double-layered {beta}-sheet structure with a hydrophobic core and one hydrophobic face. The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-{beta} units with their hydrophobic faces juxtaposed.
