哺乳动物RNA聚合酶II预启动复合物的结构
Shintaro Aibara1, Sandra Schilbach1, Patrick Cramer2
1Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Nature
|April 26, 2021
概括
研究人员可视化了前启动复合体 (PIC) 结构,揭示了转录因子TFIIH如何扭曲DNA,在细胞发育过程中打开基因调节的促进体.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 转录启动对于调节哺乳动物细胞中的基因活性至关重要.
- 预启动复合体 (PIC),包括RNA聚合酶II (Pol II) 和一般的转录因子,组装成开放的促销者DNA.
- 之前的研究确定了酵母和人类PIC的结构以及TFIIH的DNA打开模型.
研究的目的:
- 确定人类PIC的高分辨率结构与封闭和开放的促销者DNA.
- 为了阐明TFIIH转位酶XPB的DNA开放机制.
主要方法:
- 使用高分辨率冷电子显微镜 (cryo-EM) 可视化PIC结构.
- 在2. 5~2. 8 Å分辨率下确定了带有封闭和开放促销者DNA的PIC结构.
- TFIIH的结构分辨率为2.9-4.0 Å,在不同转位状态下捕获XPB.
主要成果:
- 使用Sus scrofa domesticus Pol II,确定了人类PIC的冷EM结构.
- 在转位前和转位后观察到TFIIH的XPB转位酶,诱导DNA扭曲.
- 显示DNA开放发生在两个步骤中,大约是TATA盒下游的30个基对,导致TFIIH脱离.
结论:
- TFIIH的XPB在DNA扭曲过程中起到关键作用.
- 两个阶段的DNA开放机制和随后的TFIIH脱离可能调节RNA链的启动.
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