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TraR 通过改变 RNA 聚合酶构象来变转录起始进行变构调节。

TraR allosterically regulates transcription initiation by altering RNA polymerase conformation.

机构信息

The Rockefeller University, New York, United States.

Department of Bacteriology, University of Wisconsin-Madison, Madison, United States.

出版信息

Elife. 2019 Dec 16;8:e49375. doi: 10.7554/eLife.49375.

DOI:10.7554/eLife.49375
PMID:31841111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6970531/
Abstract

TraR and its homolog DksA are bacterial proteins that regulate transcription initiation by binding directly to RNA polymerase (RNAP) rather than to promoter DNA. Effects of TraR mimic the combined effects of DksA and its cofactor ppGpp, but the structural basis for regulation by these factors remains unclear. Here, we use cryo-electron microscopy to determine structures of RNAP, with or without TraR, and of an RNAP-promoter complex. TraR binding induced RNAP conformational changes not seen in previous crystallographic analyses, and a quantitative analysis revealed TraR-induced changes in RNAP conformational heterogeneity. These changes involve mobile regions of RNAP affecting promoter DNA interactions, including the βlobe, the clamp, the bridge helix, and several lineage-specific insertions. Using mutational approaches, we show that these structural changes, as well as effects on σ region 1.1, are critical for transcription activation or inhibition, depending on the kinetic features of regulated promoters.

摘要

TraR 和其同源物 DksA 是细菌蛋白，通过直接与 RNA 聚合酶（RNAP）结合而不是与启动子 DNA 结合来调节转录起始。TraR 的作用类似于 DksA 及其辅助因子 ppGpp 的综合作用，但这些因素的调节的结构基础仍不清楚。在这里，我们使用低温电子显微镜来确定带有或不带有 TraR 的 RNAP 以及 RNAP-启动子复合物的结构。TraR 结合诱导了以前晶体学分析中未观察到的 RNAP 构象变化，并且定量分析显示 TraR 诱导了 RNAP 构象异质性的变化。这些变化涉及影响启动子 DNA 相互作用的 RNAP 的可移动区域，包括β叶、夹、桥螺旋和几个谱系特异性插入物。通过突变方法，我们表明这些结构变化以及对σ区域 1.1 的影响对于转录激活或抑制至关重要，具体取决于受调控启动子的动力学特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ea4/6970531/87789d158d7e/elife-49375-fig8.jpg
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