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：22
页码：14126-14131
DOI：10.1073/pnas.212206899
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Previously, we have studied the minimal oligomer size of an aggregate amyloid seed and the mechanism of seed growth with a multilayer {beta}-sheet model. Under high temperature simulation conditions, our approach can test the stability of possible amyloid forms. Here, we report our study of oligomers of Alzheimer's amyloid {beta}-peptide (A{beta}) fragments 16-22, 16-35, and 10-35 (abbreviated A{beta}16-22, A{beta}16-35, and A{beta}10-35, respectively). Our simulations indicate that an antiparallel {beta}-sheet orientation is the most stable for the A{beta}16-22, in agreement with a solid state NMR-based model [Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., et al. (2000) Biochemistry 39, 13748-13759]. A model with twenty-four A{beta}16-22 strands indicates a highly twisted fibril. Whereas the short A{beta}16-22 and A{beta}24-36 may exist in fully extended form, the linear parallel {beta}-sheets for A{beta}16-35 appear impossible, mainly because of the polar region in the middle of the 16-35 sequence. However, a bent double-layered hairpin-like structure (called hook) with the polar region at the turn forms parallel {beta}-sheets with higher stability. An intra-strand salt-bridge (D23-K28) stabilizes the bent hairpin-like hook structure. The bent double-{beta}-sheet model for the A{beta}10-35 similarly offers oligomer stability.
