A non-haem iron centre in the transcription factor NorR senses nitric oxide

Benoît D'Autréaux, Nicholas P Tucker, Ray Dixon, Stephen Spiro

Research output: Contribution to journalLetter

202 Citations (Scopus)

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.
LanguageEnglish
Pages769-772
Number of pages4
JournalNature
Volume437
Issue number7059
DOIs
Publication statusPublished - 29 Sep 2005

Fingerprint

Nitric Oxide
Transcription Factors
Iron
Reactive Nitrogen Species
Flavoproteins
Enterobacteriaceae
DNA-Directed RNA Polymerases
Eukaryota
Nitric Oxide Synthase
NAD
Transcriptional Activation
Adenosine Triphosphatases
Carrier Proteins
Proteins
Escherichia coli
Genes

Keywords

  • adenosine triphosphatases
  • DNA-directed RNA polymerases
  • electron spin resonance spectroscopy
  • escherichia coli
  • escherichia coli proteins
  • bacterial gene expression regulation
  • heme
  • iIron
  • genetic models
  • nitric oxide
  • genetic promoter regions
  • trans-activators
  • transcriptional activation

Cite this

D'Autréaux, Benoît ; Tucker, Nicholas P ; Dixon, Ray ; Spiro, Stephen. / A non-haem iron centre in the transcription factor NorR senses nitric oxide. In: Nature. 2005 ; Vol. 437, No. 7059. pp. 769-772.
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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.",
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A non-haem iron centre in the transcription factor NorR senses nitric oxide. / D'Autréaux, Benoît; Tucker, Nicholas P; Dixon, Ray; Spiro, Stephen.

In: Nature, Vol. 437, No. 7059, 29.09.2005, p. 769-772.

Research output: Contribution to journalLetter

TY - JOUR

T1 - A non-haem iron centre in the transcription factor NorR senses nitric oxide

AU - D'Autréaux, Benoît

AU - Tucker, Nicholas P

AU - Dixon, Ray

AU - Spiro, Stephen

PY - 2005/9/29

Y1 - 2005/9/29

N2 - 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.

AB - 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.

KW - adenosine triphosphatases

KW - DNA-directed RNA polymerases

KW - electron spin resonance spectroscopy

KW - escherichia coli

KW - escherichia coli proteins

KW - bacterial gene expression regulation

KW - heme

KW - iIron

KW - genetic models

KW - nitric oxide

KW - genetic promoter regions

KW - trans-activators

KW - transcriptional activation

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