转录启动复杂结构阐明DNA开放
C Plaschka1, M Hantsche1, C Dienemann1
1Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
Nature
|May 20, 2016
概括
研究人员使用冷电子显微镜可视化酵母转录启动复合体. 他们揭示了DNA如何在基因激活过程中打开和被捕获,为转录启动提供了一个统一的模型.
科学领域:
- 分子生物学
- 结构生物学
- 遗传学
背景情况:
- 细胞基因转录启动涉及RNA聚合酶 (Pol) II复合体组合和促进基因的开放.
- 了解这一过程的精确结构机制对于解读基因调节至关重要.
研究的目的:
- 确定酵母转录启动复合物的高分辨率结构在不同的DNA状态 (封闭和开放).
- 阐明在转录启动过程中控制DNA定位,开放和模板链载荷的分子相互作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得酵母启动复合物的结构.
- 关闭和开放DNA复合体的高分辨率结构数据 (8.8 Å和3.6 Å) 得到了实现.
主要成果:
- 详细的结构揭示了TATA盒结合蛋白 (TBP) 和转录因子 (TFIIA,TFIIB,TFIIE,TFIIF) 在Pol II裂中如何定位和保留DNA.
- 在Pol II和TFIIE的"延伸翼螺旋"域附近观察到DNA开口,独立于TFIIH.
- 通过重新定位阻碍蛋白质元素,TFIIE的"E-Ribbon"域的结可能会促进模板链的加载.
结论:
- 提出了一种转录启动的统一模型,强调通过广泛的蛋白质-DNA和蛋白质-蛋白质接触捕获开放促销者DNA.
- 这些发现为真核生物基因转录的早期事件提供了关键的结构洞察力.
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