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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 13; pp. 5010 - 5015
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 26.03.2013; National Acad Sciences; National Academy of Sciences, Washington, DC (United States)
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Benzoquinones - chemistry; Benzoquinones - metabolism; Biological Sciences; Deoxyribonucleic acid; Dimers; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; Electrons; Gene expression regulation; Gene Expression Regulation, Bacterial - physiology; Genes; Humans; Hydrogen bonds; Macrophages; Molecules; Protein Processing, Post-Translational - physiology; Protein Structure, Quaternary; Protein Structure, Tertiary; Quinones; Regulator genes; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction - physiology; Staphylococcus aureus; Staphylococcus aureus - chemistry; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Staphylococcus infections
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1219446110

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.