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

Publication Type:

Journal Article


Proc Natl Acad Sci U S A, Volume 110, Issue 13, p.5010-5 (2013)


Bacterial Proteins, Benzoquinones, DNA, Bacterial, Gene Expression Regulation, Bacterial, Humans, Protein Processing, Post-Translational, Protein Structure, Quaternary, Protein Structure, Tertiary, Repressor Proteins, Signal Transduction, Staphylococcus aureus


<p>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.</p>