We explored the influence of D₂O on the fibrillation kinetics and structural dynamics of amyloid intrinsically disordered proteins (IDPs), including α-synuclein, amyloid-β 1–42, and K18. Our findings revealed that fibrillation of IDPs was accelerated in D₂O compared to that in H₂O, exhibiting faster kinetics in contrast to the structured protein, insulin. Structural investigations using electrospray ionization ion mobility mass spectrometry and small-angle X-ray scattering combined with molecular dynamics simulations demonstrated that IDPs did not show significant structural changes that could influence accelerated fibrillation in D₂O. Umbrella sampling of protein protofibrils verified that an increased level of hydrogen bonding of D₂O and enhanced hydrophobic interactions stabilized β-sheet structured fibrils in D₂O. These findings indicate that stabilizing β-sheet fibrils and a more hydrophobic microenvironment in D₂O result in enhanced and faster fibrillation of IDPs. The study highlights the importance of considering D₂O’s differential impact on protein interactions when conducting structural and kinetic analyses, particularly for native peptides and proteins.

中文翻译：

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重水中内在无序蛋白的加速淀粉样蛋白聚集动力学


我们探讨了 D₂O 对淀粉样蛋白固有无序蛋白 （IDP） 的纤颤动力学和结构动力学的影响，包括 α-突触核蛋白、淀粉样蛋白-β 1-42 和 K18。我们的研究结果表明，与 H₂O 相比，D₂O 中 IDPs 的纤颤加速，与结构蛋白胰岛素相比，表现出更快的动力学。使用电喷雾电离离子迁移质谱和小角 X 射线散射结合分子动力学模拟的结构研究表明，IDP 没有表现出可能影响 D₂O 加速纤颤的显着结构变化。蛋白质原纤维的伞式采样证实，D₂O 氢键水平的增加和疏水相互作用的增强稳定了 D 2 中的 β 片状结构原纤维O.这些发现表明，稳定的 β 片原纤维和 D₂O 中更疏水的微环境导致 IDP 的原纤化增强和更快。该研究强调了在进行结构和动力学分析时考虑 D₂O 对蛋白质相互作用的不同影响的重要性，特别是对于天然肽和蛋白质。