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Data from: Site-specific structural order in Alzheimer’s Aβ42 fibrils

Citation

Wang, Hongsu; Lee, Yoon Kyung; Xue, Christine; Guo, Zhefeng (2018), Data from: Site-specific structural order in Alzheimer’s Aβ42 fibrils, Dryad, Dataset, https://doi.org/10.5061/dryad.768dk4s

Abstract

Deposition of amyloid fibrils is a pathological hallmark of Alzheimer’s disease. Aβ42 is the major protein whose aggregation leads to the formation of these fibrils. Understanding the detailed structure of Aβ42 fibrils is of particular importance for delineating the mechanism of Aβ42 aggregation and developing specific amyloid-targeting drugs. Here we use site-directed spin labeling and electron paramagnetic resonance spectroscopy to study the site-specific structural order at each and every residue position in Aβ42 fibrils. Strong interactions between spin labels indicate highly ordered protein backbone at the labeling site, while weak interactions suggest disordered local structure. Our results show that Aβ42 consists of 5 β-strands (residues 2-7, 10-13, 17-20, 31-36, 39-41), 3 turns (residues 7-8, 14-16, 37-38), and 1 ordered loop (residues 21-30). Spin labels introduced at β-strand sites show strong spin-spin interactions, while spin labels at turn or loop sites show weak interactions. However, residues 24, 25, and 28 also show strong interactions between spin labels, suggesting that the loop 21-30 is partly ordered. In the context of recent structural work using solid-state NMR and cryoEM, the site-specific structural order revealed in this study provides a different perspective on backbone and side chain dynamics of Aβ42 fibrils.

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