解析： - 原文“Molecular Insights into Human Serum Albumin as a Receptor of Amyloid-β in the Extracellular Region.”中，关键词“Molecular Insights”，通常被译为“分子见解”；“Human Serum Albumin”，译为“人血清白蛋白”；“Amyloid-β”，通常译为“β-淀粉样蛋白”；“Extracellular Region”，通常译为“细胞外区域”。 - 译文“解析：- 原文“Molecular Insights into Human Serum Albumin as a Receptor of Amyloid-β in the Extracellular Region.”中，关键词“Molecular Insights”，通常被译为“分子见解”；“Human Serum Albumin”，译为“人血清白蛋白”；“Amyloid-β”，通常译为“β-淀粉样蛋白”；“Extracellular Region”，通常译为“细胞外区域”。- 译文” 分子见解：人血清白蛋白作为细胞外区域中β-淀粉样蛋白的受体
Molecular Insights into Human Serum Albumin as a Receptor of Amyloid-β in the Extracellular Region.
机构信息
Department of Chemistry, Korea University , Seoul 02841, Republic of Korea.
Department of Chemistry, Pohang University of Science and Technology (POSTECH) , Pohang 37673, Republic of Korea.
出版信息
J Am Chem Soc. 2017 Nov 1;139(43):15437-15445. doi: 10.1021/jacs.7b08584. Epub 2017 Oct 10.
Regulation of amyloid-β (Aβ) aggregation by metal ions and proteins is essential for understanding the pathology of Alzheimer's disease (AD). Human serum albumin (HSA), a regulator of metal and protein transportation, can modulate metal-Aβ interactions and Aβ aggregation in human fluid; however, the molecular mechanisms for such activities remain unclear. Herein, we report the molecular-level complexation between Zn(II), Cu(II), Aβ, and HSA, which is able to alter the aggregation and cytotoxicity of Aβ peptides and induce their cellular transportation. In addition, a single Aβ monomer-bound HSA is observed with the structural change of Aβ from a random coil to an α-helix. Small-angle X-ray scattering (SAXS) studies indicate that Aβ-HSA complexation causes no structural variation of HSA in solution. Conversely, ion mobility mass spectrometry (IM-MS) results present that Aβ prevents the shrinkage of the V-shaped groove of HSA in the gas phase. Consequently, for the first time, HSA is demonstrated to predominantly capture a single Aβ monomer at the groove using the phase transfer of a protein heterodimer from solution to the gas phase. Moreover, HSA sequesters Zn(II) and Cu(II) from Aβ while maintaining Aβ-HSA interaction. Therefore, HSA is capable of controlling metal-free and metal-bound Aβ aggregation and aiding the cellular transportation of Aβ via Aβ-HSA complexation. The overall results and observations regarding HSA, Aβ, and metal ions advance our knowledge of how protein-protein interactions associated with Aβ and metal ions could be linked to AD pathogenesis.
金属离子和蛋白质对淀粉样蛋白-β（Aβ）聚集的调节对于理解阿尔茨海默病（AD）的病理学至关重要。人血清白蛋白（HSA）是金属和蛋白质运输的调节剂，能够调节人液中金属-Aβ 相互作用和 Aβ 聚集；然而，这种活性的分子机制尚不清楚。在此，我们报告了 Zn(II)、Cu(II)、Aβ 和 HSA 之间的分子级复合物形成，该复合物能够改变 Aβ 肽的聚集和细胞毒性，并诱导其细胞运输。此外，观察到一个 Aβ 单体结合 HSA，导致 Aβ 结构从无规卷曲转变为α-螺旋。小角 X 射线散射（SAXS）研究表明，Aβ-HSA 复合物形成不会导致 HSA 在溶液中的结构变化。相反，离子淌度质谱（IM-MS）结果表明，Aβ 防止了 HSA 在气相中 V 形槽的收缩。因此，首次证明 HSA 主要通过蛋白质异二聚体从溶液到气相的相转移，在沟槽中捕获单个 Aβ 单体。此外，HSA 从 Aβ 中螯合 Zn(II)和 Cu(II)，同时保持 Aβ-HSA 相互作用。因此，HSA 能够通过 Aβ-HSA 复合物形成控制无金属和金属结合的 Aβ 聚集，并协助 Aβ 的细胞运输。关于 HSA、Aβ 和金属离子的总体结果和观察结果，推进了我们对与 Aβ 和金属离子相关的蛋白质-蛋白质相互作用如何与 AD 发病机制相关的认识。
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