title: Two distinct mechanisms of transcriptional regulation by the redox sensor YodB.
abstract: For bacteria, cysteine thiol groups in proteins are commonly used as thiol-based switches for redox sensing to activate specific detoxification pathways and restore the redox balance. Among the known thiol-based regulatory systems, the MarR/DUF24 family regulators have been reported to sense and respond to reactive electrophilic species, including diamide, quinones, and aldehydes, with high specificity. Here, we report that the prototypical regulator YodB of the MarR/DUF24 family from Bacillus subtilis uses two distinct pathways to regulate transcription in response to two reactive electrophilic species (diamide or methyl-p-benzoquinone), as revealed by X-ray crystallography, NMR spectroscopy, and biochemical experiments. Diamide induces structural changes in the YodB dimer by promoting the formation of disulfide bonds, whereas methyl-p-benzoquinone allows the YodB dimer to be dissociated from DNA, with little effect on the YodB dimer. The results indicate that B. subtilis may discriminate toxic quinones, such as methyl-p-benzoquinone, from diamide to efficiently manage multiple oxidative signals. These results also provide evidence that different thiol-reactive compounds induce dissimilar conformational changes in the regulator to trigger the separate regulation of target DNA. This specific control of YodB is dependent upon the type of thiol-reactive compound present, is linked to its direct transcriptional activity, and is important for the survival of B. subtilis This study of B. subtilis YodB also provides a structural basis for the relationship that exists between the ligand-induced conformational changes adopted by the protein and its functional switch.
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: Sang Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: In-Gyun
authors.initials: IG
authors.lastname: Lee
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Kim
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Eun
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea;
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea;
authors.forename: Susanna
authors.initials: S
authors.lastname: Chae
authors.affiliation: Laboratory of Biophysics, School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea; Institute of Microbiology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea;
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Song
authors.affiliation: Laboratory of Biophysics, School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea; Institute of Microbiology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea;
authors.forename: Sa-Ouk
authors.initials: SO
authors.lastname: Kang
authors.affiliation: Department of Molecular Science and Technology & College of Pharmacy, Ajou University, Suwon, Kyeonggi 443-749, Republic of Korea;
authors.forename: Min-Duk
authors.initials: MD
authors.lastname: Seo
authors.affiliation: Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea;
authors.forename: Hyoun Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, 534-2 Yeonsu-dong, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Sung Jean
authors.initials: SJ
authors.lastname: Park
authors.affiliation: The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea; lbj@nmr.snu.ac.kr.
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003958:Diamide / Q000737:chemistry / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D010084:Oxidation-Reduction; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D016227:Benzoquinones; D003958:Diamide; C042889:2-methyl-1,4-benzoquinone
keywords: MarR/DUF24; YodB; reactive electrophilic species; redox signaling; transcriptional regulator