解决NFκB异构体结合悖论:压力和挫折指导二元转录因子的结合
Davit A Potoyan1,2, Carlos Bueno2, Weihua Zheng2
1Department of Chemistry, Iowa State University , Ames, Iowa 50011, United States.
Journal of the American Chemical Society
|November 30, 2017
概括
的NFκB家族
科学领域:
- 分子生物学
- 生物物理
- 基因组学
背景情况:
- 细胞转录因子通常作为寡合体起作用,影响基因调节.
- 核因子kappa B (NFκB) 家族包括参与细胞过程的关键转录因子.
- NFκB二元体具有不同的DNA结合亲和力和调节作用.
研究的目的:
- 研究NFκB二元体之间的差异性DNA结合亲和力的分子基础.
- 阐明NFκB同型和异型分子的结合和解结合机制的结构和能量因素.
- 了解蛋白质结构如何决定基因调节中的转录因子功能.
主要方法:
- 使用能源景观工具进行计算分析.
- 使用预测能量景观的模拟.
- 从笛卡尔坐标和物理接触的波动中提取主要组成部分.
主要成果:
- NFκB p65p50异构体比p50p50和p65p65同构体具有更强的DNA结合.
- 异构体接口中的挫折增强了构造性可塑性,从而改善了DNA的适应性.
- 在NFκB二元体中,弹性能量和机械应变是可量化的,并影响结合/解结合的动态.
结论:
- 分子架构,特别是接口挫折,决定了NFκB二元DNA结合亲和力.
- 形态塑性和机械性质是转录因子-DNA相互作用的关键决定因素.
- 了解这些能量贡献,可以了解NFκB二次体对基因的精确调节.
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