在纤维粉样蛋白-β [Aβ(1-40) ] 蛋白质中Cu2+结合的局部结构和全球模式
William A Gunderson1, Jessica Hernández-Guzmán, Jesse W Karr
1Department of Physics, Emory University, Atlanta, Georgia 30322, USA.
Journal of the American Chemical Society
|October 10, 2012
概括
阿尔茨海默病的粉样β纤维细胞通过胺残留物结合铜离子 (Cu2+). 这种结合抑制了有害的反应性氧物种的产生,这表明在基于氧化还原技术的潜在应用.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 材料科学 材料科学 材料科学
背景情况:
- 阿尔茨海默病 (AD) 涉及粉样β (Aβ) 斑块的形成.
- 铜离子 (Cu2+) 在Aβ斑块中很丰富,但它们在阿尔茨海默病发病过程中的作用尚未完全理解.
研究的目的:
- 描述Cu2+在纤维状Aβ中的协调结构 (一至四十).
- 研究Cu2+结合对Aβ纤维的氧化还原活性的影响.
主要方法:
- 高分辨率脉冲电子偏磁共振 (EPR) 光谱.
- 在全长的Aβ1-40) 纤维素中Cu2+协调的表征.
主要成果:
- 确定了一个bis-cis-histidine (His) 的赤道Cu2+协调几何.
- 证明了所有三种N端His残留物与Cu2+的结合.
- 提出了一种沿纤维轴交替 Cu2+ 结合点的模型.
结论:
- 纤维状Aβ结构抑制了Cu2+/Cu+氧化还原循环和反应性氧物种 (ROS) 生产.
- Cu2+-Aβ纤维结构可能适用于可切换的电子电荷/自旋合和氧化还原活性.
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