Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, 200032, Shanghai, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2020 Dec 8;11(1):6284. doi: 10.1038/s41467-020-20134-y.
The MerR-family proteins represent a unique family of bacteria transcription factors (TFs), which activate transcription in a manner distinct from canonical ones. Here, we report a cryo-EM structure of a B. subtilis transcription activation complex comprising B. subtilis six-subunit (2αββ'ωε) RNA Polymerase (RNAP) core enzyme, σ, a promoter DNA, and the ligand-bound B. subtilis BmrR, a prototype of MerR-family TFs. The structure reveals that RNAP and BmrR recognize the upstream promoter DNA from opposite faces and induce four significant kinks from the -35 element to the -10 element of the promoter DNA in a cooperative manner, which restores otherwise inactive promoter activity by shortening the length of promoter non-optimal -35/-10 spacer. Our structure supports a DNA-distortion and RNAP-non-contact paradigm of transcriptional activation by MerR TFs.
MerR 家族蛋白代表了一类独特的细菌转录因子（TFs），它们以不同于经典方式激活转录。在这里，我们报告了一个枯草芽孢杆菌转录激活复合物的冷冻电镜结构，该复合物包含枯草芽孢杆菌六亚基（2αββ'ωε）RNA 聚合酶（RNAP）核心酶、σ、启动子 DNA 和配体结合的枯草芽孢杆菌 BmrR，BmrR 是 MerR 家族 TFs 的原型。该结构揭示了 RNAP 和 BmrR 从相反的面识别上游启动子 DNA，并以协同的方式从 -35 元件诱导到启动子 DNA 的 -10 元件四个显著的扭曲，从而通过缩短非最佳 -35/-10 间隔的启动子长度来恢复原本无活性的启动子活性。我们的结构支持了 MerR TFs 通过 DNA 扭曲和 RNAP 非接触的转录激活模式。
