Lee Myeongsang, Kim Jae In, Na Sungsoo, Eom Kilho
Institute of Advanced Machinery Design Technology, Korea University, Seoul 02481, Republic of Korea.
Department of Mechanical Engineering, Korea University, Seoul 02481, Republic of Korea.
Phys Chem Chem Phys. 2018 Mar 28;20(13):8951-8961. doi: 10.1039/C7CP05072K.
Amyloid β (Aβ) aggregates, which are a hallmark for neurodegenerative disease, are formed through a self-assembly process such as aggregation of Aβ peptide chains. This aggregation process depends on the solvent conditions under which the proteins are aggregated. Nevertheless, the underlying mechanism of the ionic effect on the formation and stability of amyloid aggregates has not been fully understood. Here, we report how metal ions play a role in the formation and stability of Aβ aggregates at different length scales, i.e. oligomers and fibrils. It is shown that the metal (i.e. zinc or copper) ion increases the stability of Aβ oligomers, whereas the metal ion reduces the stability of Aβ fibrils. In addition, we found that zinc ions are able to more effectively destabilize fibril structures than copper ions. Metal ion-mediated (de)stabilization of Aβ oligomers (or fibrils) is attributed to the critical effect of the metal ion on the β-sheet rich crystalline structure of the amyloid aggregate and the status of hydrogen bonds within the aggregate. Our study sheds light on the role of the metal ion in stabilizing the amyloid oligomers known as a toxic agent (to functional cells), which is consistent with clinical observation that high concentrations of metal ions are found in patients suffering from neurodegenerative diseases.
淀粉样β蛋白（Aβ）聚集体是神经退行性疾病的一个标志，它通过诸如Aβ肽链聚集等自组装过程形成。这种聚集过程取决于蛋白质聚集时的溶剂条件。然而，离子对淀粉样聚集体形成和稳定性的潜在影响机制尚未完全了解。在此，我们报告了金属离子如何在不同长度尺度（即寡聚体和原纤维）上对Aβ聚集体的形成和稳定性发挥作用。结果表明，金属（即锌或铜）离子增加了Aβ寡聚体的稳定性，而金属离子降低了Aβ原纤维的稳定性。此外，我们发现锌离子比铜离子更能有效地破坏原纤维结构的稳定性。金属离子介导的Aβ寡聚体（或原纤维）的（去）稳定作用归因于金属离子对淀粉样聚集体富含β-折叠的晶体结构以及聚集体内氢键状态的关键影响。我们的研究揭示了金属离子在稳定被认为是（对功能细胞）有毒剂的淀粉样寡聚体中的作用，这与临床观察结果一致，即在患有神经退行性疾病的患者中发现高浓度的金属离子。
