叉头转录因子的新折叠和翅膀结构有助于DNA结合
George L Wang1, Yibei Jiang1, Yuying Sun2
1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, United States.
Nucleic acids research
|September 24, 2025
概括
我们确定了酵母Fkh1DNA结合域的晶体结构,揭示了一个新的蛋白质折叠. 这种结构解释了Fkh1蛋白如何与DNA相互作用,对其在细胞循环动态中的功能至关重要.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 酵母遗传学 酵母遗传学
背景情况:
- 叉头同源1 (Fkh1) 是酵母转录因子,对细胞循环调节至关重要.
- 了解Fkh1DNA结合的结构基础是阐明其调节机制的关键.
研究的目的:
- 确定Fkh1DNA结合域 (DBD) 与其目标DNA序列结合的共同晶体结构.
- 描述Fkh1.1的新型蛋白质折叠和DNA相互作用模式.
- 为了研究Fkh1的结构特征的体内功能意义.
主要方法:
- 与19-bp寡核酸一起对Fkh1-DBD进行共结晶.
- 通过X射线衍射和结构分析来确定3D结构.
- 在体内酵母补充测定与Fkh1突变.
- 分子动力学模拟.分子动力学模拟.
主要成果:
- Fkh1-DBD表现出独特的翅膀螺旋折叠,与其他叉头蛋白质不同.
- 具体的相互作用包括α-螺旋H3结合DNA大沟和Wing1/Wing2通过DNA形状与小沟相互作用.
- 翼2的新型构造,带有α螺旋H5/H6,为侧边DNA相互作用创造了一个重要的稳定循环.
- 突变分析和模拟证实了翅膀残留对Fkh1活动的功能重要性.
结论:
- 新的Fkh1折叠为其DNA结合特异性提供了结构基础,包括侧边区域偏好.
- 对Fkh1独特的折叠和DNA相互作用的结构洞察力为其他DNA结合蛋白的基于结构的设计提供了潜力.
- 在体内,Fkh1的功能与其翅膀残留的形状灵活性直接相关.
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