在bHLH-PAS域转录因子复合体中比较PAS域合的内在动态
Karthik Sudarsanam1, Ashutosh Srivastava1, Sandhya P Tiwari2
1Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat, India.
Biophysical journal
|November 2, 2025
概括
基本螺旋-循环-螺旋 Per-Arnt-Sim (bHLH-PAS) 转录因子
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 基本螺旋-循环-螺旋 Per-Arnt-Sim (bHLH-PAS) 转录因子调节重要的细胞过程.
- 尽管PAS域在结构上保持了保守,但在不同的TF复合体中表现出不同的交互接口.
- 这些接口差异对PAS域动态的影响尚不清楚.
研究的目的:
- 在各种bHLH-PAS TF复合体中对PAS域动态进行比较分析.
- 调查内在动力学是如何受到内部架构和伙伴蛋白相互作用的影响.
- 通过其动态特性探索bHLH-PAS TFs的功能多样化.
主要方法:
- 基于全原子弹性网络模型 (ENM) 的正常模式分析.
- 分子动力学模拟.分子动力学模拟.
- 使用基于投影的方法进行域-域合运动分析.
主要成果:
- 在PAS领域的自我合运动比单独的序列或结构更保守.
- 直接合的动作反映了特定的环境对伴侣蛋白的影响.
- 层次聚类揭示了CLOCK:BMAL1类型和HIF:ARNT类型复合体的独特动态分组,从序列/结构上看不出.
- 一般来说,PAS-B域比PAS-A域更不灵活.
- 在PAS-B领域的高直接合灵活性表明在交互界面上的合动态.
结论:
- PAS域的动态是由内在的架构和复杂的特定相互作用形成的.
- ENM和合运动分析有效地捕捉了生物相关的动态,即使对于AlphaFold3模型结构.
- 独特的动态配置文件有助于bHLH-PAS转录因子的功能多样化.
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