| Autor: |
Shafrir, Yinon, Durell, Stewart R., Anishkin, Andriy, Guy, H. Robert |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
|
| Popis: |
Both soluble and membrane-bound pre-fibrillar assemblies of Abeta (Aβ) peptides have been associated with Alzheimer's disease (AD). The size and nature of theses assemblies vary greatly and are affected by many factors. Here we present models of soluble hexameric assemblies of Aβ42 and suggest how they can lead to larger assemblies and eventually to fibrils. The common element in most of these assemblies is a six-stranded β-barrel formed by the last third of Aβ42, which is composed of hydrophobic residues and glycines. The hydrophobic core β-barrels of the hexameric models are shielded from water by the N-terminus and central segments. These more hydrophilic segments were modeled to have either predominantly β or predominantly α secondary structure. Molecular dynamics simulations were performed to analyze stabilities of the models. The hexameric models were used as starting points from which larger soluble assemblies of 12 and 36 subunits were modeled. These models were developed to be consistent with numerous experimental results. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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