期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 131, 期 49, 页码 17843-17852出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja905457d
关键词
-
资金
- National Institute of Health [R01 GM076688-05]
- Boston University's Center for Computational Science
Aggregation of Amyloid beta (A beta) peptide has been linked to the neurodegenerative Alzheimer's Disease and implicated in other amyloid diseases including cerebral amyloid angiopathy. A beta peptide is generated by cleavage of the amyloid precursor protein (APP) by transmembrane proteases. It is crucial to determine the structures of beta-amyloid peptides in a membrane to provide a molecular basis for the cleavage mechanism. We report the structures of amyloid beta peptide (A beta(1-40) and A beta(1-42)) as well as the 672-726 fragment of APP (referred to as A beta(1-55)) in a membrane environment determined by replica-exchange molecular dynamics simulation. A beta(1-40) is found to have two helical domains A (13-22) and B(30-35) and a type I beta-turn at 23-27. The peptide is localized at the interface between membrane and: solvent. Substantial fluctuations in domain A are observed. The dominant simulated tertiary structure of A beta(1-40) is observed to be similar to the simulated A beta(1-42) structure. However, there are differences observed in the overall conformational ensemble, as characterized by the two-dimensional free energy surfaces. The fragment of APP (A beta(1-55)) is observed to have a long transmembrane helix. The position of the transmembrane region and ensemble of membrane structures are elucidated. The conformational transition between the transmembrane A beta(1-55) structure, prior to cleavage, and the A beta(1-40) structure, following cleavage, is proposed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据