title: RegB kinase activity is repressed by oxidative formation of cysteine sulfenic acid.
abstract: RegB/RegA comprise a global redox-sensing signal transduction system utilized by a wide range of proteobacteria to sense environmental changes in oxygen tension. The conserved cysteine 265 in the sensor kinase RegB was previously reported to form an intermolecular disulfide bond under oxidizing conditions that converts RegB from an active dimer into an inactive tetramer. In this study, we demonstrate that a stable sulfenic acid (-SOH) derivative also forms at Cys-265 in vitro and in vivo when RegB is exposed to oxygen. This sulfenic acid modification is reversible and stable in the air. Autophosphorylation assay shows that reduction of the SOH at Cys-265 to a free thiol (SH) can increase RegB kinase activity in vitro. Our results suggest that a sulfenic acid modification at Cys-265 performs a regulatory role in vivo and that it may be the major oxidation state of Cys-265 under aerobic conditions. Cys-265 thus functions as a complex redox switch that can form multiple thiol modifications in response to different redox signals to control the kinase activity of RegB.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Cheng
authors.forename: Khalilah
authors.initials: K
authors.lastname: Reddie
authors.forename: Kate
authors.initials: K
authors.lastname: Carroll
authors.forename: Loubna A
authors.initials: LA
authors.lastname: Hammad
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Karty
authors.forename: Carl E
authors.initials: CE
authors.lastname: Bauer
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D019921:Biotinylation; D003545:Cysteine / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic; D000071677:Histidine Kinase; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D016354:Rhodobacter capsulatus / Q000201:enzymology; D015398:Signal Transduction; D013434:Sulfenic Acids / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013997:Time Factors; D014451:Ubiquinone / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C091081:RegB protein, Rhodobacter; D013434:Sulfenic Acids; D013438:Sulfhydryl Compounds; D014451:Ubiquinone; D011494:Protein Kinases; D000071677:Histidine Kinase; D003545:Cysteine; D010100:Oxygen