title: Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR.
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.
authors.affiliation: Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Ji
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Haihua
authors.initials: H
authors.lastname: Liang
authors.forename: Hoonsik
authors.initials: H
authors.lastname: Cho
authors.forename: Pedro
authors.initials: P
authors.lastname: Brugarolas
authors.forename: Yihe N
authors.initials: YN
authors.lastname: Gao
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Lefu
authors.initials: L
authors.lastname: Lan
authors.forename: Taeok
authors.initials: T
authors.lastname: Bae
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016227:Benzoquinones; D004269:DNA, Bacterial; D012097:Repressor Proteins; C004532:quinone