在瘤抑制剂p53的内在无序的交换活化域内对链运动的远程调制
Jenifer K Lum1, Hannes Neuweiler, Alan R Fersht
1Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom.
Journal of the American Chemical Society
|December 20, 2011
概括
这种瘤抑制剂是p53.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 蛋白质动力学 蛋白质动力学
背景情况:
- 瘤抑制剂p53蛋白在细胞调节中至关重要.
- 它的内在无序的N端域 (p53-TAD) 与众多的合作伙伴相互作用.
- 像MDM2这样的绑定伙伴可以在p53-TAD中诱导局部结构.
研究的目的:
- 为了研究p53-TAD.中的细分链运动.
- 了解蛋白质结合和酸化如何影响这些运动.
- 探索p53-TAD对监管修改的动态反应.
主要方法:
- 使用了福斯特共振能量转移 (FRET) -光相关谱 (FCS).
- 研究了p53-TAD.内的四个连续段的循环闭合动力学.
- 分析了MDM2结合和酸化对链动态的影响.
主要成果:
- p53-TAD表现出多指数动力学,偏离了一个随机卷轴模型.
- MDM2结合和酸化改变了链内动力学模式.
- 在绑定和酸化后,在偏远地区观察到链运动的意想不到的变化.
结论:
- 像p53-TAD这样的内在无序域具有复杂的结构动态.
- 合作伙伴结合和翻译后修改可以在这些领域内诱导长期相互作用.
- 这些发现揭示了p53功能更复杂的调节机制.
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