NtrC

NtrC (nitrogen regulatory protein C) is a bacterial transcriptional regulator, a member of the NtrC family of enhancer-binding proteins that activate transcription from sigma-54-dependent promoters. It forms part of the NtrB-NtrC two-component system, where NtrB is the sensor kinase that responds to nitrogen availability and transfers a phosphate to NtrC.

Upon nitrogen limitation, NtrB autophosphorylates and transfers the phosphate to an aspartate residue in the N-terminal receiver domain of NtrC. Phosphorylation triggers conformational changes that promote dimerization and assembly of higher-order oligomers containing the central AAA+ ATPase domain. The C-terminal DNA-binding domain recognizes specific enhancer sequences located upstream of sigma-54 promoters. The activated NtrC interacts with the sigma-54 RNA polymerase holoenzyme via the GAFTGA loop in the AAA+ domain, hydrolyzing ATP to remodel the promoter and initiate transcription. This cascade upregulates genes involved in nitrogen uptake and assimilation, such as amtB (ammonium transporter) and glnA (glutamine synthetase), among others in the nitrogen regulon.

Structural organization: NtrC proteins typically have three domains: an N-terminal receiver (response regulator) domain with a conserved aspartate, a central AAA+ ATPase domain, and a C-terminal helix-turn-helix DNA-binding domain. This architecture is common to other bacterial enhancer-binding proteins that activate sigma-54-dependent transcription.

Distribution: NtrC homologs are widespread in proteobacteria and other bacteria, where they coordinate nitrogen metabolism with environmental cues.