通过综合建模和聚类来确定4E-BP2蛋白的结构性倾向
Thomas E Tsangaris1,2, Spencer Smyth1,2, Gregory-Neal W Gomes1,2
1Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7, Canada.
The journal of physical chemistry. B
|August 18, 2023
概括
本质上是混乱的4E-BP2蛋白质.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 4E-BP2蛋白质本质上是无序的,通过与真核生物启动因子4E (eIF4E) 相互作用来调节mRNA翻译.
- 4E-BP2的酸化改变了它的结构,通过稳定与结合不相容的折叠域来降低对eIF4E的结合亲和力.
研究的目的:
- 为了生成和分析非酸化 (NP) 和五倍酸化 (5P) 4E-BP2 的构造组合.
- 阐明链内相互作用在4E-BP2的折叠和结合动态中的作用.
主要方法:
- 使用了基于罗塞塔的采样算法,该算法针对内在无序区域 (IDR) 进行了优化.
- 使用综合贝叶斯方法与实验数据 (NMR,SAXS,smFRET) 相结合.
- 应用聚合层次的分类集群来分析构造集群.
主要成果:
- NP状态显示了由电荷分离和远距离区域之间的pi相互作用驱动的接触.
- 5P状态表现出明显的相互作用,N端IDR (N-IDR) 在折叠域中与酸盐 (pT37,pT46) 接触.
- 根据C端IDR (C-IDR) 和N-IDR相互作用,确定了一个与eIF4E结合兼容的NP集群,并根据C端IDR (C-IDR) 和N-IDR相互作用区分了5P集群.
结论:
- 提供了对NP和5P 4E-BP2的构造集的详细结构见解.
- 揭示了链内相互作用和酸化偏差蛋白质折叠和eIF4E结合的方式.
- 通过4E-BP2.2对翻译调节的结构机制产生了可伪造的假设.
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