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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.