Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, USA.
J Biol Chem. 2012 Nov 2;287(45):37703-12. doi: 10.1074/jbc.M112.388611. Epub 2012 Sep 18.
Mycobacterium tuberculosis thrives in oxidative environments such as the macrophage. To survive, the bacterium must sense and adapt to the oxidative conditions. Several antioxidant defenses including a thick cell wall, millimolar concentrations of small molecule thiols, and protective enzymes are known to help the bacterium withstand the oxidative stress. However, oxidation-sensing regulators that control these defenses have remained elusive. In this study, we report a new oxidation-sensing regulator, Rv1049 or MosR (M. tuberculosis oxidation-sensing regulator). MosR is a transcriptional repressor of the MarR family, which, similarly to Bacillus subtilis OhrR and Staphylococcus aureus MgrA, dissociates from DNA in the presence of oxidants, enabling transcription. MosR senses oxidation through a pair of cysteines near the N terminus (Cys-10 and Cys-12) that upon oxidation forms a disulfide bond. Disulfide formation rearranges a network of hydrogen bonds, which leads to a large conformational change of the protein and dissociation from DNA. MosR has been shown previously to play an important role in survival of the bacterium in the macrophage. In this study, we show that the main role of MosR is to up-regulate expression of rv1050 (a putative exported oxidoreductase that has not yet been characterized) in response to oxidants and propose that it is through this role that MosR contributes to the bacterium survival in the macrophage.
结核分枝杆菌在巨噬细胞等氧化环境中茁壮成长。为了生存，细菌必须感知并适应氧化条件。已知几种抗氧化防御机制，包括厚细胞壁、毫摩尔浓度的小分子硫醇和保护性酶，有助于细菌抵御氧化应激。然而，控制这些防御机制的氧化感应调节剂仍然难以捉摸。在这项研究中，我们报告了一种新的氧化感应调节剂，即 Rv1049 或 MosR（结核分枝杆菌氧化感应调节剂）。MosR 是 MarR 家族的转录抑制剂，类似于枯草芽孢杆菌 OhrR 和金黄色葡萄球菌 MgrA，在氧化剂存在下与 DNA 解离，从而实现转录。MosR 通过位于 N 端附近的一对半胱氨酸（Cys-10 和 Cys-12）感应氧化，形成二硫键。二硫键的形成重新排列了氢键网络，导致蛋白质发生大的构象变化并与 DNA 解离。先前已经表明 MosR 在细菌在巨噬细胞中的存活中起着重要作用。在这项研究中，我们表明 MosR 的主要作用是在氧化剂的作用下上调 rv1050（一种尚未被表征的假定分泌氧化还原酶）的表达，并提出正是通过这种作用，MosR 有助于细菌在巨噬细胞中的存活。
