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Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR
- Ji, Quanjiang, Zhang, Liang, Jones, Marcus B., Sun, Fei, Deng, Xin, Liang, Haihua, Cho, Hoonsik, Brugarolas, Pedro, Gao, Yihe N., Peterson, Scott N., Lan, Lefu, Bae, Taeok, He, Chuan
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.13 pp. 5010-5015
- DNA, Staphylococcus aureus, genes, humans, menadione, pathogens, stress response, transcription (genetics), transcription factors
- 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° rigid-body rotation as well as a 9-Å 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.