Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR
Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR
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DOI：
10.1073/pnas.1219446110
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发表时间：
2013-03-26
影响因子：
11.1
通讯作者：
He, Chuan
中科院分区：
文献类型：
--
作者：
Ji, Quanjiang;Zhang, Liang;He, Chuan
苯二酚分子是细胞内电子传递载体，也是细胞内和细胞外的关键信号。然而，目前对苯二酚信号的转录调控及其分子基础知之甚少。在这里，我们发现了一个硫醇应激敏感调节因子YodB家族转录调节因子，它是金黄色葡萄球菌对苯二酚应激反应的中心成分，我们称之为对苯二酚敏感和反应抑制因子(QsrR)。我们还发现并证实了一种基于基本残基Cys-5的S-醌化的前所未有的对苯二酚的传感机制。QsrR-DNA和QsrR-甲二酮复合体的结构表征进一步表明，甲萘二酮的共价缔合直接导致QsrR从操纵子DNA中释放，经过10度刚体旋转和二聚体亚基之间9埃的伸长。这种对苯二酚敏感的转录调控因子的分子水平特征为研究人类病原体中由苯二酚介导的基因调控提供了重要的见解。
Quinone molecules are intracellular electron-transport carriers, as well as critical intra-and extracellular signals. However, transcriptional regulation of quinone signaling and its molecular basis are poorly understood. Here, we identify a thiol-stress-sensing regulator YodB family transcriptional regulator as a central component of quinone stress response of Staphylococcus aureus, which we have termed the quinone-sensing and response repressor (QsrR). We also identify and confirm an unprecedented quinone-sensing mechanism based on the S-quinonization of the essential residue Cys-5. Structural characterizations of the QsrR-DNA and QsrR-menadione complexes further reveal that the covalent association of menadione directly leads to the release of QsrR from operator DNA following a 10 degrees rigid-body rotation as well as a 9-angstrom elongation between the dimeric subunits. The molecular level characterization of this quinone-sensing transcriptional regulator provides critical insights into quinone-mediated gene regulation in human pathogens.