Transcriptional regulation by the dedicated nitric oxide sensor, NorR: a route towards NO detoxification.
A flavorubredoxin and its associated oxidoreductase (encoded by norV and norW respectively) detoxify NO (nitric oxide) to form N2O (nitrous oxide) under anaerobic conditions in Escherichia coli. Transcription of the norVW genes is activated in response to NO by the σ54-dependent regulator and dedicated NO sensor, NorR, a member of the bacterial enhancer-binding protein family. In the absence of NO, the catalytic activity of the central ATPase domain of NorR is repressed by the N-terminal regulatory domain that contains a non-haem iron centre. Binding of NO to this centre results in the formation of a mononitrosyl iron species, enabling the activation of ATPase activity. Our studies suggest that the highly conserved GAFTGA loop in the ATPase domain, which engages with the alternative σ factor σ54 to activate transcription, is a target for intramolecular repression by the regulatory domain. Binding of NorR to three conserved enhancer sites upstream of the norVW promoter is essential for transcriptional activation and promotes the formation of a stable higher-order NorR nucleoprotein complex. We propose that enhancer-driven assembly of this oligomeric complex, in which NorR apparently forms a DNA-bound hexamer in the absence of NO, provides a 'poised' system for transcriptional activation that can respond rapidly to nitrosative stress.
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney NR4 7UH, UK. matt.bush@bbsrc.ac.uk
Matthew
M
Bush
Tamaswati
T
Ghosh
Nicholas
N
Tucker
Xiaodong
X
Zhang
Ray
R
Dixon
D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D011487:Protein Conformation; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D029968:Escherichia coli Proteins; C504602:NorR protein, E coli; D015534:Trans-Activators; D009569:Nitric Oxide