Sox2 DNA 结合域的溶液结构揭示了 DNA 结合中的 conformational 选择
Andrea Orsetti1, Jonathan Slejfer1, Satine Ha1
1NMR Spectroscopy Group, Bijvoet Centre for Biomolecular Research, Utrecht University, Utrecht, CH 3854, The Netherlands.
Nucleic acids research
|November 5, 2025
概括
这种转录因子是Sox2 .
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- Sox2是调节细胞多能性的关键转录因子.
- 了解Sox2的自由状态动态和DNA识别至关重要,但仍然具有挑战性.
研究的目的:
- 阐明Sox2DNA结合域 (DBD) 的溶液结构和构造动力学.
- 为了研究Sox2的DNA识别和结合接口的机制.
主要方法:
- 解决方案核磁共振 (NMR) 光谱学. 解决方案核磁共振 (NMR) 光谱学.
- 分子动力学模拟.分子动力学模拟.
- 进行NMR定位实验.
主要成果:
- Sox2 DBD的螺旋核心在溶液中结构良好,类似于其DNA结合状态.
- 蛋白质存在于折叠和部分展开状态之间的平衡状态,由高离子强度稳定.
- Sox2的DNA结合接口用于特定和非特定的DNA重叠,特定结合涉及C端尾部刚性化.
结论:
- 在DNA结合之前,Sox2的DBD是预折叠和稳定的,这表明一种构造性选择机制.
- 这种预折叠状态有助于从DNA扫描到特定结合的快速过渡.
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