蛋白质活动通过 conformational 的调节
Shiou-Ru Tzeng1, Charalampos G Kalodimos
1Department of Chemistry & Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Nature
|July 18, 2012
概括
蛋白质动力学,不仅仅是结构,也决定了功能. 结构和内部运动的变化调节了蛋白质 - 连接体相互作用,影响了催化剂激活剂蛋白质变体中的DNA结合亲和力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物物理学 分子生物物理学
背景情况:
- 蛋白质功能由静态结构和动态内部运动之间的复杂相互作用来调节.
- 现有的模型往往无法解释仅基于结构数据的功能变化,突出显示了理解动态贡献的差距.
- 内部蛋白质动态在调节生物活动中的定量作用在很大程度上仍然难以捉摸.
研究的目的:
- 研究蛋白质内部动力学的变化,特别是 conformational entropy,如何影响蛋白质-连接体相互作用.
- 阐明快速和缓慢的内部动态对蛋白质结合活性的定量贡献.
- 为了确定 conformational 变化是否可以决定绑定事件,即使具有相同的绑定接口.
主要方法:
- 利用核磁共振 (NMR) 光谱分析结构和动态变化.
- 研究了DNA与各种代体激活蛋白 (CAP) 变体的结合,具有不同活跃和不活跃状态的种群.
- 集成的NMR数据与热力学测量.
主要成果:
- 证明了构造变化会显著影响蛋白质-连接体结合亲和力,即使结合接口结构相同.
- 在CAP变体中观察到DNA结合亲缘关系的明显差异,尽管保留了结合接口.
- 表明,根据蛋白质变体的动态状态,形态可以抑制或刺激结合.
结论:
- 形态,衡量快速的内部动态,在调节蛋白质-连接体相互作用方面发挥着关键作用.
- 缓慢的内部动态,涉及能量激发的构造状态,也有助于约束性调节.
- 仅仅从基态结构无法完全预测蛋白质结合活性;内部动力学是关键的调节者.
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