title: A non-haem iron centre in the transcription factor NorR senses nitric oxide.
abstract: Nitric oxide (NO), synthesized in eukaryotes by the NO synthases, has multiple roles in signalling pathways and in protection against pathogens. Pathogenic microorganisms have apparently evolved defence mechanisms that counteract the effects of NO and related reactive nitrogen species. Regulatory proteins that sense NO mediate the primary response to NO and nitrosative stress. The only regulatory protein in enteric bacteria known to serve exclusively as an NO-responsive transcription factor is the enhancer binding protein NorR (refs 9, 10-11). In Escherichia coli, NorR activates the transcription of the norVW genes encoding a flavorubredoxin (FlRd) and an associated flavoprotein, respectively, which together have NADH-dependent NO reductase activity. The NO-responsive activity of NorR raises important questions concerning the mechanism of NO sensing. Here we show that the regulatory domain of NorR contains a mononuclear non-haem iron centre, which reversibly binds NO. Binding of NO stimulates the ATPase activity of NorR, enabling the activation of transcription by RNA polymerase. The mechanism of NorR reveals an unprecedented biological role for a non-haem mononitrosyl-iron complex in NO sensing.
authors.affiliation: John Innes Centre, Colney, Norwich NR4 7UH, UK.
authors.forename: Benoît
authors.initials: B
authors.lastname: D'Autréaux
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tucker
authors.forename: Ray
authors.initials: R
authors.lastname: Dixon
authors.forename: Stephen
authors.initials: S
authors.lastname: Spiro
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006418:Heme; D007501:Iron / Q000378:metabolism*; D008957:Models, Genetic; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D029968:Escherichia coli Proteins; C504602:NorR protein, E coli; D015534:Trans-Activators; D009569:Nitric Oxide; D006418:Heme; D007501:Iron; D012321:DNA-Directed RNA Polymerases; D000251:Adenosine Triphosphatases