Structural Insights into the Eukaryotic Transcription Initiation Machinery.

Structural Insights into the Eukaryotic Transcription Initiation Machinery.
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DOI:
10.1146/annurev-biophys-070816-033751
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发表时间:
2017-05-22
影响因子:
12.4
通讯作者:
He Y
He Y
中科院分区:
生物学1区
文献类型:
--
作者:
Nogales E;Louder RK;He Y

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真核基因转录需要在启动子处组装一个大型预起始复合物 (PIC),其中包括 RNA 聚合酶 II (Pol II) 和通用转录因子 TFIID、TFIIA、TFIIB、TFIIF、TFIIE 和 TFIIH。 Pol II、TFIID 和 T FIIH 的大小和复杂性阻碍了它们从异源系统的重建,并且纯化依赖于稀缺的内源来源。加上它们的构象灵活性和相互作用的瞬时性,这些限制阻碍了 PIC 的结构表征。然而,在过去几年中,冷冻电子显微镜 (cryo-EM) 的进步使得以越来越高的分辨率对不同功能状态下的大型 PIC 组件进行可视化成为可能。这些结构现在可以以接近原子的细节进行解释,并为过去和未来的功能研究提供令人兴奋的结构框架,使我们对转录起始的复杂过程有独特的机制洞察。
Eukaryotic gene transcription requires the assembly at the promoter of a large preinitiation complex (PIC) that includes RNA polymerase II (Pol II) and the general transcription factors TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. The size and complexity of Pol II, TFIID, and T FIIH have precluded their reconstitution from heterologous systems, and purification relies on scarce endogenous sources. Together with their conformational flexibility and the transient nature of their interactions, these limitations had precluded structural characterization of the PIC. In the last few years, however, progress in cryo-electron microscopy (cryo-EM) has made possible the visualization, at increasingly better resolution, of large PIC assemblies in different functional states. These structures can now be interpreted in near-atomic detail and provide an exciting structural framework for past and future functional studies, giving us unique mechanistic insight into the complex process of transcription initiation.
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