Structural insights into preinitiation complex assembly on core promoters
Structural insights into preinitiation complex assembly on core promoters
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DOI：
10.1126/science.aba8490
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发表时间：
2021-04-30
期刊：
影响因子：
56.9
通讯作者：
Xu, Yanhui
中科院分区：
文献类型：
--
作者：
Chen, Xizi;Qi, Yilun;Xu, Yanhui
转录因子IID（TFIID）识别核心启动子并支持RNA聚合酶II（Pol II）介导的真核转录的前起始复合物（PIC）组装。我们确定了人类TFIID为基础的PIC在三个逐步组装状态的结构，并揭示了双轨PIC组装：逐步启动子沉积Pol II和广泛的模块化重组轨道I（TATA-TFIID结合元件启动子）与直接启动子沉积轨道II（TATA-只有和TATA-少启动子）。这两个轨道在相同构象中会聚在类似于50-亚基全PIC处，由此TFIID稳定PIC组织并支持将细胞周期蛋白依赖性激酶（CDK）活化激酶（CAK）加载到Pol II上以及Pol II羧基末端结构域的CAK介导的磷酸化。出乎意料的是，TFIID的TBP类似地弯曲PIC中的TATA盒和无TATA启动子。我们的研究提供了高度多样化的启动子上的逐步PIC组装的结构可视化。
Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase II (Pol II)-mediated eukaryotic transcription. We determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-TFIID-binding element promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at an similar to 50-subunit holo PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading of cyclin-dependent kinase (CDK)activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of the Pol II carboxyl-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.