Cross-Strand Pairing and Amyloid Assembly

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• 作者：Yan Liang ; Sai Venkatesh Pingali ; Ashutosh S. Jogalekar ; James P. Snyder ; Pappannan Thiyagarajan ; David G. Lynn
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：September 23, 2008
• 年：2008
• 卷：47
• 期：38
• 页码：10018-10026
• 全文大小：583K
• 年卷期：v.47,no.38(September 23, 2008)
• ISSN：1520-4995

文摘

Amino acid cross-strand pairing interactions along a β-sheet surface have been implicated in protein β-structural assembly and stability, yet the relative contributions have been difficult to evaluate directly. Here we develop the central core sequence of the Aβ peptide associated with Alzheimer’s disease, Aβ(16−22), as an experimental system for evaluating these interactions. The peptide allows for internal comparisons between electrostatic and steric interactions within the β-sheet and an evaluation of these cross-strand pair contributions to β-sheet registry. A morphological transition from fibers to hollow nanotubes arises from changes in β-sheet surface complementarity and provides a convenient indicator of the β-strand strand registry. The intrinsic β-sequence and pair correlations are critical to regulate secondary assembly. These studies provide evidence for a critical desolvation step that is not present in most models of the nucleation-dependent pathway for amyloid assembly.