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：2000
卷号：97
期号：24
页码：13045-13050
DOI：10.1073/pnas.230315097
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue {beta}-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended {beta}-sheet structure for Alzheimer's {beta}-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the {beta}-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) 13C NMR technique, that probe the {beta}-sheet organization in fibrils formed by the full-length, 40-residue {beta}-amyloid peptide (A{beta}1-40). Although an antiparallel {beta}-sheet organization often is assumed and is invoked in recent structural models for full-length {beta}-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length {beta}-amyloid fibrils and applies MQNMR to a significant problem in structural biology.
