Western Seoul Center, Korea Basic Science Institute, Seoul 120-140 (Korea).
Angew Chem Int Ed Engl. 2015 Jan 26;54(5):1561-4. doi: 10.1002/anie.201410389. Epub 2014 Dec 10.
Copper-amyloid peptides are proposed to be the cause of Alzheimer's disease, presumably by oxidative stress. However, mice do not produce amyloid plaques and thus do not suffer from Alzheimer's disease. Although much effort has been focused on the structural characterization of the copper- human amyloid peptides, little is known regarding the copper-binding mode in murine amyloid peptides. Thus, we investigated the structure of copper-murine amyloid peptides through multi-frequency, multi-technique pulsed EPR spectroscopy in conjunction with specific isotope labeling. Based on our pulsed EPR results, we found that Ala2, Glu3, His6, and His14 are directly coordinated with the copper ion in murine amyloid β peptides at pH 8.5. This is the first detailed structural characterization of the copper-binding mode in murine amyloid β peptides. This work may advance the knowledge required for developing inhibitors of Alzheimer's disease.
铜-淀粉样肽被认为是阿尔茨海默病的病因，可能是通过氧化应激。然而，老鼠不会产生淀粉样斑块，因此不会患阿尔茨海默病。尽管人们已经投入了大量精力来研究铜-人淀粉样肽的结构特征，但对于鼠淀粉样肽中的铜结合模式知之甚少。因此，我们通过多频、多技术脉冲 EPR 光谱结合特异性同位素标记研究了铜-鼠淀粉样肽的结构。基于我们的脉冲 EPR 结果，我们发现在 pH 值为 8.5 时，Ala2、Glu3、His6 和 His14 直接与鼠淀粉样β肽中的铜离子配位。这是对鼠淀粉样β肽中铜结合模式的首次详细结构特征研究。这项工作可能会推进开发阿尔茨海默病抑制剂所需的知识。
