Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status.
The Escherichia coli transcription factor OxyR is activated by the formation of an intramolecular disulfide bond and subsequently is deactivated by enzymatic reduction of the disulfide bond. Here we show that OxyR can be activated by two possible pathways. In mutants defective in the cellular disulfide-reducing systems, OxyR is constitutively activated by a change in the thiol-disulfide redox status in the absence of added oxidants. In wild-type cells, OxyR is activated by hydrogen peroxide. By monitoring the presence of the OxyR disulfide bond after exposure to hydrogen peroxide in vivo and in vitro, we also show that the kinetics of OxyR oxidation by low concentrations of hydrogen peroxide is significantly faster than the kinetics of OxyR reduction, allowing for transient activation in an overall reducing environment. We propose that the activity of OxyR in vivo is determined by the balance between hydrogen peroxide levels and the cellular redox environment.
Aslund
F
F
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Zheng
M
M
Beckwith
J
J
Storz
G
G
D000469:Alkaline Phosphatase / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005838:Genotype; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C499299:oxyR protein, E coli; D006861:Hydrogen Peroxide; D000469:Alkaline Phosphatase; D005978:Glutathione; D019803:Glutathione Disulfide