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PROSITE documentation PDOC00861 [for PROSITE entry PS01117]

MarR-type HTH domain signature and profile





Description

The marR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 135 amino acids present in transcription regulators of the marR/slyA family, involved in the development of antibiotic resistance. This family of transcription regulators is named after Escherichia coli marR, a repressor of genes which activate the multiple antibiotic resistance and oxidative stress regulons, and after slyA from Salmonella typhimurium and E. coli, a transcription regulator that is required for virulence and survival in the macrophage environment. Regulators with the marR-type HTH domain are present in bacteria and archaea and control a variety of biological functions, including resistance to multiple antibiotics, household disinfectants, organic solvents, oxidative stress agents and regulation of the virulence factor synthesis in pathogens of humans and plants. Many of the marR-like regulators respond to aromatic compounds [1,2,3].

The crystal structures of marR, mexR and slyA have been determined and show a winged HTH DNA-binding core flanked by helices involved in dimerization (see <PDB:1LJ9>). The DNA-binding domains are ascribed to the superfamily of winged helix proteins, containing a three (four)-helix (H) bundle and a three-stranded antiparallel β-sheet (B) in the topology: H1-(H1')-H2-B1-H3-H4-B2-B3-H5-H6. Helices 3 and 4 comprise the helix-turn-helix motif and the β-sheet is called the wing. Helix 4 is termed the recognition helix, like in other HTHs where it binds the DNA major groove. The helices 1, 5 and 6 are involved in dimerization, as most marR-like transcription regulators form dimers [3,4,5].

Some proteins known to contain a marR-type HTH domain:

  • Escherichia coli marR, a transcription repressor of chromosomal multiple antibiotic resistance (mar) in diverse bacteria [1,4].
  • Salmonella typhimurium and E. coli slyA, a transcription activator for molecular chaperones, proteins involved in acid resistance and in virulence and a repressor for the expression of several biosynthetic enzymes.
  • Pseudomonas aeruginosa mexR, a transcription repressor of the mexAB-oprM multidrug efflux operon, a major determinant for broad resistance. The allosteric mechanism for the regulation of DNA binding seems to differ from that of marR [5].
  • Rhodopseudomonas palustris badR, a transcription activator for the anaerobic degradation of benzoate [2].
  • Escherichia coli mprA (emrR), a repressor of the multidrug resistance pump emrAB operon.
  • Erwinia chrysanthemi pecS, a transcription regulator for synthesis of pectinase, cellulase and other key factors for plant infection.
  • Bacillus subtilis hpr, a repressor of protease production and sporulation.
  • Butyrivibrio fibrisolvens cinR, a transcription repressor of cinnamoyl ester hydrolase for ruminal degradation of plant material.

As a signature pattern, we have selected a 34 residue segment showing high conservation within this family. This conserved region from helix 3 to strand 3 is located in the DNA binding domain. We also developed a profile that covers the entire wHTH, including helix 1 and the conserved part of helix 6, and which allows a more sensitive detection.

Last update:

April 2006 / Pattern revised.

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Technical section

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

HTH_MARR_1, PS01117; MarR-type HTH domain signature  (PATTERN)

HTH_MARR_2, PS50995; MarR-type HTH domain profile  (MATRIX)


References

1AuthorsAlekshun M.N. Levy S.B.
TitleThe mar regulon: multiple resistance to antibiotics and other toxic chemicals.
SourceTrends Microbiol. 7:410-413(1999).
PubMed ID10498949

2AuthorsEgland P.G. Harwood C.S.
TitleBadR, a new MarR family member, regulates anaerobic benzoate degradation by Rhodopseudomonas palustris in concert with AadR, an Fnr family member.
SourceJ. Bacteriol. 181:2102-2109(1999).
PubMed ID10094687

3AuthorsWu R.Y. Zhang R.G. Zagnitko O. Dementieva I. Maltzev N. Watson J.D. Laskowski R. Gornicki P. Joachimiak A.
TitleCrystal structure of Enterococcus faecalis SlyA-like transcriptional factor.
SourceJ. Biol. Chem. 278:20240-20244(2003).
PubMed ID12649270
DOI10.1074/jbc.M300292200

4AuthorsAlekshun M.N. Levy S.B. Mealy T.R. Seaton B.A. Head J.F.
TitleThe crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution.
SourceNat. Struct. Biol. 8:710-714(2001).
PubMed ID11473263
DOI10.1038/90429

5AuthorsLim D. Poole K. Strynadka N.C.J.
TitleCrystal structure of the MexR repressor of the mexRAB-oprM multidrug efflux operon of Pseudomonas aeruginosa.
SourceJ. Biol. Chem. 277:29253-29259(2002).
PubMed ID12034710
DOI10.1074/jbc.M111381200



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