在α-Synuclein Amyloid 形成过程中的电荷调节
Tinna Pálmadóttir1, Anders Malmendal1,2, Thom Leiding1
1Department of Biochemistry and Structural Biology, Lund University, P.O. Box 124, 221 00, Lund, Sweden.
Journal of the American Chemical Society
|May 17, 2021
概括
在α-synuclein纤维的形成过程中,质子吸收导致pH值显著增加. 这种pH转移会改变明显的pKa值,特别是在C端尾部.
科学领域:
- 生物化学
- 生物物理
- 结构生物学
背景情况:
- 静电相互作用对于蛋白质的功能至关重要.
- 测量pKa扰动揭示了蛋白质复合体形成和自我组合过程中的静电效应,例如粉样纤维.
- 对于高分子量粉样纤维素,使用溶液NMR测定特定位点的pKa很困难.
研究的目的:
- 在α-synuclein纤维形成过程中调查pH变化和pKa扰动.
- 了解静电相互作用和质子吸收在粉体生成中的作用.
主要方法:
- 使用pH电极测量,光指示器颜色测量和溶液NMR光谱来监测pH变化.
- 使用大都会蒙特卡洛模拟来模拟纤维形成期间的质子吸收.
- 研究了一个突变的α-synuclein与C终端电荷删除.
主要成果:
- 在α-synuclein纤维的形成过程中观察到显著的pH值增加 (0. 9单位,从5. 6到6. 5),表明质子吸收.
- 计算出至少1.1个单位的平均明显pKa的酸性残留.
- 证明C终端删除突变显示较小的pH增加和pKa转移.
- 模拟证实了纤维细胞形成期间的质子吸收,并显示了质子结合电容的变化.
结论:
- 在α-synuclein纤维的形成过程中发生质子吸收.
- 观察到的pH上升和pKa变化与C端尾的高酸残留密度有关.
- 静电相互作用,特别是涉及C端尾部,在纤维形成过程中起着关键作用.
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