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CueR DNA-binding transcriptional dual regulator

Synonyms: CueR-Ag, CuerR-Au, CueR, CueR-Cu+
The Cu efflux regulator , CueR, regulates genes related to the primary copper homeostasis system [2, 3, 5, 6] in response to the presence of copper, silver, or gold ions [5, 7, 8].
The crystal structures of CueR dimers bound to Cu+, Ag+, or Au+ have been solved [1]. Each monomer consists of three domains, an N-terminal DNA-binding domain carrying two helix-turn-helix motifs, a central dimerization domain, and a C-terminal metal-binding domain. The DNA-binding and dimerization domains are characteristic of the MerR family of proteins. The dimerization domain contains a 10-turn α-helix that forms an antiparallel coiled-coil with the helix of the other monomer. The metal-binding domain contains an unusual metal receptor site in which the bound metal is inaccessible to the solvent. The metal ion is bound with a linear coordination to two conserved cysteine residues. This dithiolate coordination confers the metal ion selectivity for +1 ions [1].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
CueR Non-Functional   Apo [IDA], [IPI] [1]
CueR-Ag Functional Allosteric Holo [IDA], [IPI] [1]
CueR-Cu+ Functional Allosteric Holo [IDA], [IPI] [1]
CuerR-Au Functional Allosteric Holo [IDA], [IPI] [1]
Evolutionary Family: MerR
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: cueR
  Genome position: 513993-514400
  Length: 408 bp / 135 aa
Operon name: cueR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) copA, cueO, moaA, moaB, moaC, moaD, moaE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
molybdenum (5)
The P-type ATPase (P-ATPase) Superfamily (1)
membrane (1)
metabolism (1)
other (mechanical, nutritional, oxidative stress) (1)
Regulated operon(s) copA, cueO, moaABCDE
First gene in the operon(s) copA, cueO, moaA
Simple and complex regulons CueR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  CueR-Cu+ activator copAp Sigma70 -25.0 -57.0 copA
511427 511445 [BPP], [HIBSCS], [SM] [2], [3], [4], [5]
  CueR-Cu+ activator cueOp nd -25.0 -63.0 cueO
137011 137029 [BPP], [GEA], [HIBSCS] [2], [5]
  CueR-Cu+ repressor moaAp1 nd 202.0 -16.0 moaA, moaB, moaC, moaD, moaE
817019 817037 [GEA], [HIBSCS] [5]

Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [BPP] Binding of purified proteins

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation

 [GEA] Gene expression analysis


 [1] Changela A., Chen K., Xue Y., Holschen J., Outten CE., O'Halloran TV., Mondragon A., 2003, Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR., Science. 301(5638):1383-7

 [2] Outten FW., Outten CE., Hale J., O'Halloran TV., 2000, Transcriptional activation of an Escherichia coli copper efflux regulon by the chromosomal MerR homologue, cueR., J Biol Chem. 275(40):31024-9

 [3] Petersen C., Moller LB., 2000, Control of copper homeostasis in Escherichia coli by a P-type ATPase, CopA, and a MerR-like transcriptional activator, CopR., Gene. 261(2):289-98

 [4] Stoyanov JV., Hobman JL., Brown NL., 2001, CueR (YbbI) of Escherichia coli is a MerR family regulator controlling expression of the copper exporter CopA., Mol Microbiol. 39(2):502-11

 [5] Yamamoto K., Ishihama A., 2005, Transcriptional response of Escherichia coli to external copper., Mol Microbiol. 56(1):215-27

 [6] Grass G., Rensing C., 2001, Genes involved in copper homeostasis in Escherichia coli., J Bacteriol. 183(6):2145-7

 [7] Stoyanov JV., Magnani D., Solioz M., 2003, Measurement of cytoplasmic copper, silver, and gold with a lux biosensor shows copper and silver, but not gold, efflux by the CopA ATPase of Escherichia coli., FEBS Lett. 546(2-3):391-4

 [8] Stoyanov JV., Brown NL., 2003, The Escherichia coli copper-responsive copA promoter is activated by gold., J Biol Chem. 278(3):1407-10

 [9] Andoy NM., Sarkar SK., Wang Q., Panda D., Benitez JJ., Kalininskiy A., Chen P., 2009, Single-molecule study of metalloregulator CueR-DNA interactions using engineered Holliday junctions., Biophys J. 97(3):844-52

 [10] Martell DJ., Joshi CP., Gaballa A., Santiago AG., Chen TY., Jung W., Helmann JD., Chen P., 2015, Metalloregulator CueR biases RNA polymerase's kinetic sampling of dead-end or open complex to repress or activate transcription., Proc Natl Acad Sci U S A. 112(44):13467-72

 [11] Rensing C., Grass G., 2003, Escherichia coli mechanisms of copper homeostasis in a changing environment., FEMS Microbiol Rev. 27(2-3):197-213

 [12] Hobman JL., Wilkie J., Brown NL., 2005, A design for life: prokaryotic metal-binding MerR family regulators., Biometals. 18(4):429-36

 [13] Brown NL., Stoyanov JV., Kidd SP., Hobman JL., 2003, The MerR family of transcriptional regulators., FEMS Microbiol Rev. 27(2-3):145-63

 [14] Rademacher C., Masepohl B., 2012, Copper-responsive gene regulation in bacteria., Microbiology. 158(Pt 10):2451-64