Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Science. 2018 Dec 21;362(6421). doi: 10.1126/science.aau8872. Epub 2018 Nov 15.
The general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy, chemical cross-linking mass spectrometry, and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA box-binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter.
一般转录因子IID（TFIID）是真核转录起始前复合物（PIC）的关键组成部分，负责识别核心启动子 DNA 并启动 PIC 组装。我们使用低温电子显微镜、化学交联质谱和生化重组来确定 TFIID 的完整分子结构，并定义 TFIID 在 TATA 盒结合蛋白（TBP）加载到启动子 DNA 过程中的构象景观。我们的结构分析显示了在 TFIIA 和启动子 DNA 存在下 TFIID 的五个结构状态，表明 TFIID 与下游启动子的初始结合使上游 DNA 定位，并促进 TBP 扫描 TATA 盒，随后与启动子结合。我们的发现为 TFIID 将 TBP 特异性加载到启动子上提供了一个机制模型。
