Stability of a Recently Found Triple-β-Stranded Aβ1–42 Fibril Motif

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• 作者：Wenhui Xi ; Wenhua Wang ; Gabrielle Abbott ; Ulrich H. E. Hansmann
• 刊名：Journal of Physical Chemistry B
• 出版年：2016
• 出版时间：May 26, 2016
• 年：2016
• 卷：120
• 期：20
• 页码：4548-4557
• 全文大小：701K
• 年卷期：0
• ISSN：1520-5207

文摘

Amyloid-β peptides form polymorphous amyloid fibrils are correlated with the pathogenesis of Alzheimer’s disease. Recently, a new ssNMR high-resolution structure has been reported for wild-type Aβ1–42 fibrils that is characterized by a strand-turn-strand-turn-strand motif instead of the U-shape form seen in previously known wild-type Aβ-fibril structures. Analyzing molecular dynamics simulations we comment on the relative weight of the new fibril structure and present evidence that its stability depends on hydrophobic contacts involving the C-terminal residues I41 and A42, but not on the salt bridge K28–A42. We further argue that Aβ1–42 peptides with this structure may assemble in fibrils with a 2-fold packing symmetry and discuss two possible arrangements.