Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR

Quanjiang Ji, Liang Zhang, Marcus B. Jones, Fei Sun, Xin Deng, Haihua Liang, Hoonsik Cho, Pedro Brugarolas, Yihe N. Gao, Scott N. Peterson, Lefu Lan, Taeok Bae, Chuan He

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5010-5015
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number13
DOIs
StatePublished - Mar 26 2013

Keywords

  • Macrophage
  • Thiol alkylation

ASJC Scopus subject areas

  • General

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    Ji, Q., Zhang, L., Jones, M. B., Sun, F., Deng, X., Liang, H., Cho, H., Brugarolas, P., Gao, Y. N., Peterson, S. N., Lan, L., Bae, T., & He, C. (2013). Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR. Proceedings of the National Academy of Sciences of the United States of America, 110(13), 5010-5015. https://doi.org/10.1073/pnas.1219446110