本质上有障碍的p53极端C端通过"飞"与S100B (betabeta) 结合
1Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA.
Journal of the American Chemical Society
|February 14, 2009
概括
内在无序的蛋白质 (IDP) 使用残留结构来实现功能. 这些结构通过调节相互作用期间折叠的性成本来调节结合热力学,不一定是结合速率.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 内在无序的蛋白质 (IDP) 缺乏稳定的三级结构,这对于它们的调节和信号功能至关重要.
- 许多内部流离失所者在不受约束状态下表现出残余结构,这些结构在与合作伙伴结合时折叠,但它们的作用尚不清楚.
研究的目的:
- 研究残留结构在内在无序蛋白 (IDP) 中的作用.
- 阐明IDP中合结合和折叠的机制.
- 确定IDPs的结合热力学中的残余结构的功能.
主要方法:
- 采用了基于物理的原子模拟.
- 计算了多维的自由能量表面,用于合折叠和结合.
- 模拟了本质上失调的p53 C端与蛋白质S100B (betabeta) 之间的相互作用.
主要成果:
- 未结合的p53样本多个折叠状态.
- 与S100B ((betabeta) 的结合是通过非特异性复合体发生的,类似于"飞"机制.
- 其余结构调节折叠的性成本,影响结合热力学.
结论:
- 在监管IDP中,残留结构的主要作用是对结合的热力学控制.
- 剩余结构不能通过作为初始接触点来提高绑定率.
- 这些发现与之前的NMR和类似系统的粗粒度建模研究一致.
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