霍克斯D9家庭主区的N端基本残留驱动其沿着DNA搜索目标部位
Siyuan Li1, Cong Li2, Lingyan Wang1
1Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, PR China.
International journal of biological macromolecules
|May 21, 2025
概括
转录因子HOXD9使用其N端臂进行DNA扩散和向结合. 带正电荷的残留物促进了DNA相互作用,揭示了HOX蛋白的保存机制.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 遗传学 是一个遗传学.
背景情况:
- HOXD9是一种HOX家族的转录因子,对索米特分化至关重要.
- HOXD9的失调与瘤发生和转移有关.
- 对于HOXD9的DNA目标搜索和相互作用的确切机制尚不清楚.
研究的目的:
- 为了阐明HOXD9在DNA上的目标搜索动态的原子级分子机制.
- 确定控制HOXD9扩散和DNA相互作用的关键调节动机.
主要方法:
- 用全原子分子动力学模拟来构建动力学模型.
- 对HOXD9主体域进行了广泛的模拟,该主体域与10bp的DNA段相互作用.
- 为了验证,进行了局部导向的突变遗传学测定和植物遗传学分析.
主要成果:
- HOXD9的N终端臂是其在特定地点向之前的DNA扩散过程的组成部分.
- 在N端的正电荷残留物 (R2-R5) 通过静电相互作用介导DNA接触.
- 对于特定的目标位置识别,HOXD9利用R5和helix-3域,N端从小槽中脱离.
结论:
- 已经建立了HOXD9的DNA目标搜索动态的详细模型.
- N端臂和特定残留物在HOXD9-DNA结合和识别中发挥着关键作用.
- 鉴定出来的机制很可能在其他家庭主体蛋白中得到保留,从而提供了对HOX家族功能的洞察力.
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