Complex System Assembly Underlies a Two-Tiered Model of Highly Delocalized Electrons
Complex System Assembly Underlies a Two-Tiered Model of Highly Delocalized Electrons
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DOI：
10.1021/acs.jpclett.6b00699
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发表时间：
2016-05-19
影响因子：
5.7
通讯作者：
Laurents, Douglas V.
中科院分区：
文献类型：
--
作者：
Mompean, Miguel;Nogales, Aurora;Laurents, Douglas V.
淀粉样原纤维是非常稳定的低聚结构，具有广泛的高度合作的氢键网络，其物理来源仍然难以捉摸。虽然非极性系统受益于氢键和疏水相互作用，我们发现，含有谷氨酰胺和天冬酰胺氨基酸残基的高极性序列形成超极化氢键。通过密度泛函理论计算观察到的这一特征编码了这些极性低聚物的高稳定性的起源。这些结果解释了复杂的淀粉样蛋白组装的理论模型的基础上产生的高度离域电子，其中之一是总是存在于极性和疏水系统中的两种不同类型的合作效应。实验电导率测量，ThT荧光增强，和NMR光谱支持这一建议，并揭示了拆卸的条件。
Amyloid fibrils are exceptionally stable oligomeric structures with extensive, highly cooperative H-bonding networks whose physical origin remains elusive. While nonpolar systems benefit from both H-bonds and hydrophobic interactions, we found that highly polar sequences containing glutamine and asparagine amino acid residues form hyperpolarized H-bonds. This feature, observed by density functional theory calculations, encodes the origin of these polar oligomers' high stability. These results are explained in a theoretical model for complex amyloid assembly based on two different types of cooperative effects resulting from highly delocalized electrons, one of which is always present in both polar and hydrophobic systems. Experimental electric conductivity measurements, ThT fluorescence enhancement, and NMR spectroscopy support this proposal and reveal the conditions for disassembly.