通过单分子光直接观察酵母蛋白Ure2的多步聚合机制
Jie Yang1,2, Alexander J Dear3, Thomas C T Michaels3,4
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , 15 Datun Road, Chaoyang District, Beijing 100101, China.
Journal of the American Chemical Society
|January 23, 2018
概括
酵母蛋白Ure2通过涉及短寿命寡合体的多步过程形成粉状纤维. 碎片化驱动自我复制,但二次核化是最小的,提供了对功能性粉体系统的见解.
科学领域:
- 生物化学
- 分子生物学
- 生物物理
背景情况:
- 聚自组合成粉样结构与神经退行性疾病和功能生物过程有关.
- 粉样蛋白形成产生了多样化的物种 (从寡合体到纤维) 具有复杂的动力关系.
- 聚合物具有自我复制和传染性.
研究的目的:
- 在酵母蛋白Ure2聚合过程中对寡合体群体进行定量表征.
- 阐明寡合体形成和耗尽的分子机制.
- 了解功能性粉体中的寡聚体,纤维和自我复制之间的关系.
主要方法:
- 用单个分子光谱来研究Ure2聚合.
- 用全球运动分析来确定寡合体的形成和转化机制.
- 进行了寡头群体及其动态的定量表征.
主要成果:
- 与纤维转化相比,大多数Ure2寡合物寿命短,解离率高.
- 一个转移稳定的寡合体转化为一个不同的寡合体,然后变成纤维.
- 纤维细胞碎片化驱动自催化自我复制;二次核化对Ure2没有意义.
结论:
- 建立了一个框架,以了解粉体系统中的寡聚体和纤维之间的时间和因果关系.
- 提供了有关功能性粉体系统无毒性的见解.
- 证明碎片化,而不是二次核化,是Ure2纤维素自我复制的关键.
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