Pathways & interactions
MerR-type HTH domain (IPR000551)
Short name: MerR-type_HTH_dom
- Putative DNA-binding domain (IPR009061)
- MerR-type HTH domain (IPR000551)
The merR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 70 residues present in the merR family of transcriptional regulators [PMID: 2492496]. MerR-type regulators are present in diverse bacterial genera, in the cytoplasm. The helix-turn-helix DNA-binding motif is located in the N-terminal part of these transcriptional regulators and is followed by a coiled-coil region. The C-terminal part of merR-type regulators contains effector binding regions that are specific to the effector recognised. Most merR-type transcriptional regulators respond to environmental stimuli, like heavy metals, oxidative stress or antibiotics and a subgroup of metalloregulators are bacterial transcription activators that respond to metal ions [PMID: 12829265].
Several structures of merR-type transcriptional regulators have been resolved and their N-terminal DNA-binding domains are ascribed to the superfamily of winged-helix proteins, containing a four-helix (H) bundle and a three-stranded antiparallel beta-sheet (B) in the topology: B1-H1-H2-B2-B3-H3-H4 [PMID: 12186881]. The helix-turn-helix motif comprises the first and second helices, the second being called the recognition helix. The HTH is involved in DNA-binding into the major groove, where the recognition helix makes most DNA-contacts. The second DNA-binding element is wing W1, composed of the second and third beta-strands and their connecting loop. The third DNA-binding element, wing W2, is not a loop like in typical winged-helix proteins, but another H-T-H motif formed by helices three and four. In a typical merR regulator, the HTH and two wings bind the promoter of the regulated operon between the -35 and -10 regions in a spacer of 19/20 bp and longer than usual, distorting the operator DNA and causing RNA polymerase to initiate transcription [PMID: 12829265]. Most merR-like transcriptional regulators are dimers.
Some proteins known to contain a merR-type HTH domain:
- Tn501 merR, mercuric resistance operon regulatory protein. In the absence of mercury merR represses transcription by binding tightly, as a dimer, to the 'mer' operator region; when mercury is present the dimeric complex binds a single ion and becomes a potent transcriptional activator, while remaining bound to the mer site.
- Bacillus subtilis bltR, bmrR and mtaN (ywnD), transcriptional activators of the blr and bmr transporters involved in multidrug resistance.
- Escherichia coli soxR, responds to oxidative stress and autoregulatory controls a superoxide response regulon.
- Bradyrhizobium japonicum nolA, a transcriptional regulator involved in the genotype-specific nodulation of soybeans.
- Streptomyces lividans tipA, a transcriptional activator which binds to and is activated by the antibiotic thiostrepton.
- Escherichia coli zntR, a zinc-responsive regulator of zntA ATPase.
- Escherichia coli cueR , a regulator of the copper efflux regulon.
- CarA (Q1DDV9) and CarH (Q1DDV8) from Myxococcus xanthus, paralogous repressors that requires B(12) to down-regulation of a light-inducible promoter [PMID: 21502508, PMID: 18315685].
- TtCarH (Q746J7) from Thermus thermophilus, belongs to a class of photoreceptors that use 5'-deoxyadenosylcobalamin (AdoB12) as the light-sensing chromophore [PMID: 23512413].