PROSITE documentation PDOC00477

MerR-type HTH domain signature and profile





Description

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. The family is named after the merR regulator of mercury resistance operons of Gram-negative bacteria found on transposons Tn21 and Tn501 [1]. 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 recognized. 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 [2].

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 β-sheet (B) in the topology: B1-H1-H2-B2-B3-H3-H4 (see <PDB:1JBG>) [3]. 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 β-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 [2]. 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.

The pattern we developed starts at position 2 of the helix-turn-helix motif and extends three residues upstream of its C-terminal extremity. We also developed a profile that covers the entire wHTH, including the first strand, H-T-H motif, wings W1 and W2 and which allows a more sensitive detection.

Last update:

October 2003 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

HTH_MERR_2, PS50937; MerR-type HTH domain profile  (MATRIX)

HTH_MERR_1, PS00552; MerR-type HTH domain signature  (PATTERN)


References

1AuthorsHelmann J.D., Wang Y., Mahler I., Walsh C.T.
TitleHomologous metalloregulatory proteins from both gram-positive and gram-negative bacteria control transcription of mercury resistance operons.
SourceJ. Bacteriol. 171:222-229(1989).
PubMed ID2492496

2AuthorsBrown N.L., Stoyanov J.V., Kidd S.P., Hobman J.L.
TitleThe MerR family of transcriptional regulators.
SourceFEMS Microbiol. Rev. 27:145-163(2003).
PubMed ID12829265

3AuthorsZheleznova-Heldwein E.E., Brennan R.G.
SourceNature 409:378-382(2001).



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