Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Chem Biol. 2021 Jan;17(1):57-64. doi: 10.1038/s41589-020-00653-x. Epub 2020 Sep 28.
The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question of which mechanism prevails, we determined two cryo-EM structures of transcription activation complexes (TAC) comprising Escherichia coli CueR (a prototype MerR TF), RNAP holoenzyme and promoter DNA. The structures reveal that this TF promotes productive promoter-polymerase association without canonical protein-protein contacts seen between other activator proteins and RNAP. Instead, CueR realigns the key promoter elements in the transcription activation complex by clamp-like protein-DNA interactions: these induce four distinct kinks that ultimately position the -10 element for formation of the transcription bubble. These structural and biochemical results provide strong support for the DNA distortion paradigm of allosteric transcriptional control by MerR TFs.
MerR 家族转录因子 (TFs) 是一大类细菌蛋白，通过结合启动子中 RNA 聚合酶结合区域的中心，对细胞内金属离子和多种抗生素做出响应。虽然大多数 TF 通过蛋白-蛋白相互作用改变转录，但 MerR TFs 能够重塑启动子 DNA。为了解决哪种机制占主导地位的问题，我们确定了包含大肠杆菌 CueR（原型 MerR TF）、RNAP 全酶和启动子 DNA 的转录激活复合物 (TAC) 的两个低温电镜结构。这些结构表明，这种 TF 促进了有生产力的启动子 - 聚合酶的结合，而不是在其他激活蛋白和 RNAP 之间看到的典型蛋白 - 蛋白接触。相反，CueR 通过类似夹子的蛋白-DNA 相互作用重新排列转录激活复合物中的关键启动子元件：这些相互作用诱导四个不同的扭曲，最终将 -10 元件定位形成转录泡。这些结构和生化结果为 MerR TFs 通过变构转录控制的 DNA 扭曲范例提供了强有力的支持。
