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

Proc Natl Acad Sci U S A, 2013/3/26;110(13):5010-5.

Ji Q[1], Zhang L, Jones MB, Sun F, Deng X, Liang H, Cho H, Brugarolas P, Gao YN, Peterson SN, Lan L, Bae T, He C

Affiliations

PMID: 23479646DOI: 10.1073/pnas.1219446110

Impact factor: 12.779

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.
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