Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 57, Issue 2, Pages 357-364Publisher
WILEY
DOI: 10.1002/prot.20222
Keywords
Alzheimer's disease; parallel beta-helix; protein threading; molecular dynamics simulation; protein structure prediction
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Funding
- NIA NIH HHS [R01AG18416, AG 2813096] Funding Source: Medline
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Amyloid fibrils, a key pathological feature of Alzheimer's disease (AD) and other amyloidosis implicated in neurodegeneration, have a characteristic cross-beta structure. Here we present a structural model for the core of amyloid fibrils formed by the Abeta peptide using computational approaches and experimental data. Abeta(15-36) was threaded against the parallel beta-helical proteins. Our multi-layer model was constructed using the top scoring template 1lxa, a left-handed parallel beta-helical protein. This six-rung helical model has in-register repeats of the Abeta(15-36) sequence. Each rung has three beta-strands separated by two turns. The model was tested using molecular dynamics simulations in explicit water, and is in good agreement with a number of experimental observations. In addition, a model based on right-handed helical proteins is also described. The core structural model described here might serve as the building block of the Abeta(1-40) amyloid fibril as well as some other amyloid fibrils. (C) 2004 Wiley-Liss, Inc.
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