InterPro domain: IPR001867

Bacteria and plants frequently use two-components signal transduction systems(TCSs) to adapt to environmental changes and to survive under stress conditions. Typical TCSs couple a transmembrane histidine protein kinase (HK), which detects changes in the environmnent, to a cytosolic response regulator (RR), which often alters gene expression. Most RRs contain two distinct domains: an N-terminal receiver domain and a C-terminal effector domain. The former autophosphorylates on a histidine residue on detecting an external stimulus. The phosphate is then transferred to an invariant aspartate residue in a highly conserved receiver domain of the response regulator. Phosphorylation activates a variable effector domain of the response regulator, which triggers the cellular response. The C-terminal effector domain contains DNA and RNA polymerase binding sites. Several dimers or monomers bind head to tail to small tandem repeats upstream of the genes. The RNA polymerase binding sites interact with the alpha or sigma subunit of RNA polymerase. The OmpR/PhoB subfamily is the largest subfamily of RRs. Members of the OmpR/PhoB subfamily include such diverse transcriptional regulators as Escherichia coli PhoB (of the phosphate assimilation pathway), Enterococcus faecium VanR (which controls resistance to the antibiotic vancomycin), and Agrobacterium tumefaciens VirG (involved in the establishment of crown gall tumors in plant. The C-terminal effector domain of the OmpR/PhoB subfamily RRs binds DNA. This DNA-binding domain is also found in proteins other than response regulators, such as Vibrio cholerea ToxR, a transmembrane protein involved in cholera toxin expression [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].

The OmpR/PhoB-type DNA-binding domain has the typical fold of the wingedhelix-turn-helix DNA-binding domain. The structure of the OmpR/PhoB-type DNA-binding domain consists of three alpha helices packed against two antiparallelbeta sheets, an N-terminal four-stranded antiparallel beta sheet and a C-terminal hairpin. The hairpin interacts with a short stretchof beta strand, that connects helices alpha1 and alpha2, to generate a three-stranded antiparallel beta sheet. The topology for the domain is beta1-beta2-beta3-beta4-alpha1-beta5-alpha2-alpha3-beta6-beta7. The hydrophobic core ofthe domain is formed by sidechains contributed by each of the seven betastrands and three alpha helices [ 8 , 8 , 8 , 8 , 8 ].

1. The DNA-binding domain of OmpR: crystal structures of a winged helix transcription factor. Structure 5, 109-24
2. Structure of the DNA-binding domain of the response regulator PhoP from Mycobacterium tuberculosis. Biochemistry 46, 14751-61
3. Response regulator YycF essential for bacterial growth: X-ray crystal structure of the DNA-binding domain and its PhoB-like DNA recognition motif. FEBS Lett. 582, 3434-8
4. Structure of the response regulator PhoP from Mycobacterium tuberculosis reveals a dimer through the receiver domain. Biochemistry 50, 5948-57
5. Structural dynamics of the two-component response regulator RstA in recognition of promoter DNA element. Nucleic Acids Res. 42, 8777-88
6. Structure/function relationships in OmpR and other winged-helix transcription factors. Curr. Opin. Microbiol. 5, 135-41
7. Structural relationships in the OmpR family of winged-helix transcription factors. J. Mol. Biol. 269, 301-12