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：1998
卷号：95
期号：23
页码：13407-13412
DOI：10.1073/pnas.95.23.13407
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa {beta}-amyloid (A{beta}) peptide. Crosslinking of A{beta} peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated A{beta}. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the A{beta} peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A{beta}. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 A. Analysis of these data establish that this central core of A{beta} consists of a parallel {beta}-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the A{beta} fibril is a hydrogen-bonded, parallel {beta}-sheet defining the long axis of the A{beta} fibril propagation.
