细胞中蛋白质折叠能量格局的时间变化
Anna Jean Wirth1, Max Platkov, Martin Gruebele
1Department of Chemistry and ‡Department of Physics and Center for Biophysics and Computational Biology, University of Illinois , Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|December 6, 2013
概括
蛋白质折叠速度和稳定性在细胞内动态变化. 酵母糖酸酶 (PGK-FRET) 折叠取决于细胞周期阶段和染色体的接近,揭示了一个随时间变化的能量格局.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 化学反应速率和自由能量通常独立于时间.
- 在体外蛋白质折叠发生在一个固定的能量格局上.
- 细胞内环境表现出动态波动,可以改变蛋白质折叠的景观.
研究的目的:
- 研究活细胞内酵母糖酸激酶 (PGK-FRET) 的时间依赖的折叠场景.
- 为了确定蛋白质折叠是否受到细胞周期和染色体接近的影响.
主要方法:
- 使用Förster共振能量转移 (FRET) 来标记和监测酵母糖酸酶 (PGK-FRET).
- 采用U2OS细胞作为细胞环境和哺乳动物细胞周期作为时间调节器.
- 测试的PGK-FRET折叠率与细胞周期阶段相关,以及与线粒染色体相对的空间位置.
主要成果:
- 发现PGK-FRET的折叠率和热力学稳定性取决于细胞周期阶段.
- 折叠速率测量了距离线粒染色体近距离的折叠速率.
- 线粒细胞的快速折叠率并不能归因于DNA丰富区域的加速折叠.
结论:
- 由细胞循环调节的细胞内环境,动态调节蛋白质折叠能量格局.
- 细胞位置,特别是靠近线粒染色体的位置,不仅仅解释了改变的折叠速率.
- 蛋白质折叠是一个动态的过程,受活细胞内的时间和空间环境的影响.
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