Self-assembly of the full-length amyloid Aβ42 protein in dimers.
Self-assembly of the full-length amyloid Aβ42 protein in dimers.
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DOI：
10.1039/c6nr06850b
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发表时间：
2016-12-07
期刊：
影响因子：
6.7
通讯作者：
Lyubchenko YL
中科院分区：
文献类型：
--
作者：
Zhang Y;Hashemi M;Lv Z;Lyubchenko YL
淀粉样蛋白（Aβ）自组装成纳米聚集体是阿尔茨海默病（AD）发展的一个标志，然而无序单体如何组装成聚集体的机制仍然难以捉摸。在这里，我们应用长时间分子动力学模拟来充分表征Aβ42单体组装成二聚体。单体在它们的相互作用过程中经历构象变化，但所得的二聚体结构不类似于原纤维结构中发现的那些。为了识别自然构象的二聚体之间的一组模拟的，验证方法的开发和应用，和一个子集的二聚体构象进行了表征。这些二聚体不包含通常在原纤维中发现的长β链。二聚体主要通过中心疏水区域和C-末端区域内的相互作用来稳定，并具有来自局部氢键的贡献。二聚体是动态的，证明了存在一组构象和二聚体解离过程的定量分析。
The self-assembly of amyloid (Aβ) proteins into nano-aggregates is a hallmark of Alzheimer’s disease (AD) development, yet the mechanism of how disordered monomers assemble into aggregates remains elusive. Here, we applied long-time molecular dynamics simulations to fully characterize the assembly of Aβ42 monomers into dimers. Monomers undergo conformational changes during their interaction, but the resulting dimer structures do not resemble those found in fibril structures. To identify natural conformations of dimers among a set of simulated ones, validation approaches were developed and applied, and a subset of dimer conformations were characterized. These dimers do not contain long β-strands that are usually found in fibrils. The dimers are stabilized primarily by interactions within the central hydrophobic regions and the C-terminal regions, with a contribution from local hydrogen bonding. The dimers are dynamic, as evidenced by the existence of a set of conformations and by the quantitative analyses of the dimer dissociation process.
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