启动器绑定TFIID的结构和人类预启动复合组件的模型
Robert K Louder1, Yuan He2,3, José Ramón López-Blanco4
1Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
Nature
|March 24, 2016
概括
一般转录因子IID (TFIID) 结构揭示了它如何结合DNA并组装转录机制. 这些发现揭示了RNA聚合酶II激活基因的基本机制.
科学领域:
- 分子生物学
- 结构生物学
- 遗传学
背景情况:
- 一般转录因子IID (TFIID) 对于启动RNA聚合酶II转录至关重要.
- TFIID是一种大型复合物,含有TATA结合蛋白 (TBP) 和13个TBP相关因子 (TAF).
- TFIID可以识别多种核心促销者DNA序列.
研究的目的:
- 确定与TFIIA结合的人类TFIID和核心促进体DNA的结构.
- 想象一个完整的人类TAF-less预启动复合体 (PIC) 的组装.
- 了解TFIID在促进者识别和转录启动中的作用.
主要方法:
- 单粒子冷电子显微镜 (cryo-EM) 在亚纳米分辨率.
- 确定人类TFIID-TFIIA促进体DNA复合物的结构.
- 使用冷EM重建人类TAF-less PIC.
主要成果:
- 该结构显示TFIID子单元与所有核心促进器元素联系,TAF1和TAF2与下游促进器相互作用.
- TFIIA 作为 TBP-TATA 综合体和 TFIID B 叶之间的桥梁.
- 对TFIID-DNA和TAF-less PIC结构的比较揭示了TFIID在PIC组装中的作用.
结论:
- TFIID在识别核心促销者DNA和核化PIC组件方面发挥着核心作用.
- 结构洞察力阐明了RNA聚合酶II的转录启动机制.
- 这些发现为了解基因调节和潜在治疗点提供了基础.
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