Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
J Mol Biol. 2012 Jun 8;419(3-4):139-57. doi: 10.1016/j.jmb.2012.03.019. Epub 2012 Mar 28.
Bacterial transcription activators regulate transcription by making essential protein-protein interactions with RNA polymerase, for example, with region 4 of the σ(70) subunit (σ(70) R4). Rob, SoxS, and MarA comprise a closely related subset of members of the AraC/XylS family of transcription factors that activate transcription of both class I and class II promoters. Recently, we showed that interactions between SoxS and σ(70) R4 occlude the binding of σ(70) R4 to the -35 promoter element of class II promoters. Although Rob shares many similarities with SoxS, it contains a C-terminal domain (CTD) that the other paralogs do not. Thus, a goal of this study was to determine whether Rob makes protein-protein interactions with σ(70) R4 at class II promoters and, if so, whether the interactions occlude the binding of σ(70) R4 to the -35 hexamer despite the presence of the CTD. We found that although Rob makes fewer interactions with σ(70) R4 than SoxS, the two proteins make the same, unusual, position-dependent interactions. Importantly, we found that Rob occludes σ(70) R4 from binding the -35 hexamer, just as does SoxS. Thus, the CTD does not substantially alter the way Rob interacts with σ(70) R4 at class II promoters. Moreover, in contrast to inferences drawn from the co-crystal structure of Rob bound to robbox DNA, which showed that only one of Rob's dual helix-turn-helix (HTH) DNA binding motifs binds a recognition element of the promoter's robbox, we determined that the two HTH motifs each bind a recognition element in vivo.
细菌转录激活因子通过与 RNA 聚合酶形成必需的蛋白质-蛋白质相互作用来调节转录,例如与σ(70)亚基的区域 4(σ(70) R4)形成相互作用。Rob、SoxS 和 MarA 构成了 AraC/XylS 家族转录因子的一个密切相关的亚组,它们可以激活 I 类和 II 类启动子的转录。最近,我们发现 SoxS 与 σ(70) R4 的相互作用会阻断 σ(70) R4 与 II 类启动子-35 启动子元件的结合。虽然 Rob 与 SoxS 有许多相似之处,但它包含一个 C 端结构域(CTD),而其他同源物则没有。因此,本研究的一个目标是确定 Rob 是否与 II 类启动子上的 σ(70) R4 形成蛋白质-蛋白质相互作用,如果是这样,即使存在 CTD,这些相互作用是否会阻断 σ(70) R4 与-35 六聚体的结合。我们发现,尽管 Rob 与 σ(70) R4 的相互作用比 SoxS 少,但这两种蛋白形成了相同的、不寻常的、位置依赖的相互作用。重要的是,我们发现 Rob 会阻断 σ(70) R4 与-35 六聚体的结合,就像 SoxS 一样。因此,CTD 并没有实质性地改变 Rob 在 II 类启动子上与 σ(70) R4 相互作用的方式。此外,与 Rob 与 robbox DNA 结合的共晶体结构所推断的结论相反,该结构表明 Rob 的两个双螺旋-转角-螺旋(HTH)DNA 结合基序仅与启动子 robbox 的一个识别元件结合,我们确定这两个 HTH 基序在体内都与一个识别元件结合。