title: Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR.
abstract: As a master redox-sensing MarR-family transcriptional regulator, AbfR participates in oxidative stress responses and virulence regulations in Staphylococcus epidermidis. Here, we present structural insights into the DNA-binding mechanism of AbfR in different oxidation states by determining the X-ray crystal structures of a reduced-AbfR/DNA complex, an overoxidized (Cys13-SO2H and Cys13-SO3H) AbfR/DNA, and 2-disulfide cross-linked AbfR dimer. Together with biochemical analyses, our results suggest that the redox regulation of AbfR-sensing displays two novel features: (i) the reversible disulfide modification, but not the irreversible overoxidation, significantly abolishes the DNA-binding ability of the AbfR repressor; (ii) either 1-disulfide cross-linked or 2-disulfide cross-linked AbfR dimer is biologically significant. The overoxidized species of AbfR, resembling the reduced AbfR in conformation and retaining the DNA-binding ability, does not exist in biologically significant concentrations, however. The 1-disulfide cross-linked modification endows AbfR with significantly weakened capability for DNA-binding. The 2-disulfide cross-linked AbfR adopts a very "open" conformation that is incompatible with DNA-binding. Overall, the concise oxidation chemistry of the redox-active cysteine allows AbfR to sense and respond to oxidative stress correctly and efficiently.
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|University of Chinese Academy of Sciences , Beijing 100049, China.
authors.forename: Guijie
authors.initials: G
authors.lastname: Liu
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|University of Chinese Academy of Sciences , Beijing 100049, China.
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Coordination Chemistry Institute and State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Georgia State University , Atlanta, Georgia 30303, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of Life Sciences, Fudan University , Shanghai 200433, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gan
authors.affiliation: Coordination Chemistry Institute and State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
authors.forename: Hao
authors.identifier: 0000-0001-8937-4946
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Lefu
authors.initials: L
authors.lastname: Lan
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Cai-Guang
authors.identifier: 0000-0001-5778-4422
authors.initials: CG
authors.lastname: Yang
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013212:Staphylococcus epidermidis / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D004220:Disulfides; D014157:Transcription Factors; D004247:DNA