RegulonDB RegulonDB 11.1:Regulon Page

NikR DNA-binding transcriptional repressor

Synonyms: NikR-Ni2+, NikR-Cd2+, NikR-Co2+, NikR-Cu+, NikR-Zn2+, NikR
NikR, "Nickel-responsive repressor," is a tetramer and consists of two domains. The crystal structures of the C-terminal domain, apo-NikR, nickel-activated NikR, and NikR in complex with its operator DNA have been solved [4, 5, 6]. The C-terminal 83 amino acids form the tetrameric core, which carries the high-affinity nickel-binding site and resembles the ACT fold of the ACT (aspartokinase, chorismate mutase, TyrA) family. Two N-terminal domains intertwine to form a dimeric DNA-binding ribbon-helix-helix (RHH) domain [1]. The two RHH DNA-binding domains flank the tetrameric core of the protein [5]. The NikR tetramer contains four high-affinity nickel-binding sites located at the subunit interfaces of the C-terminal domain and additional low-affinity metal-binding sites [5, 7, 8, 9, 10, 11]. The coordination of the nickel ion binding to the high-affinity site depends on binding to DNA. The nickel ion is bound in a four-coordinate planar conformation to NikR in solution and in a six-coordinate conformation to NikR bound to DNA [12].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
NikR Functional Allosteric Holo nd nd nd
NikR-Cd2+ Functional Allosteric Holo nd nd nd
NikR-Co2+ Functional Allosteric Holo nd nd nd
NikR-Cu+ Functional Allosteric Holo nd nd nd
NikR-Ni2+ Functional   Apo nd nd nd
NikR-Zn2+ Functional Allosteric Holo nd nd nd
Evolutionary Family: CopG
TFBs length: 28
TFBs symmetry: inverted-repeat
Connectivity class: Local Regulator
Gene name: nikR
  Genome position: 3618588-3618989
  Length: 402 bp / 133 aa
Operon name: nikABCDER
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) nikA, nikB, nikC, nikD, nikE, nikR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
ABC superfamily, membrane component (2)
membrane (2)
aerobic respiration (2)
anaerobic respiration (2)
ABC superfamily ATP binding cytoplasmic component (2)
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Regulated operon(s) nikABCDER
First gene in the operon(s) nikA
Simple and complex regulons FNR,NarL,NikR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor regulation    

Transcription factor binding sites (TFBSs) arrangements

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  NikR-Ni2+ repressor nikAp1 nd -12.5 -51.5 nikA, nikB, nikC, nikD, nikE, nikR
3613602 3613630 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] nd [1], [2], [3]

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


 [1] Chivers PT., Sauer RT., 1999, NikR is a ribbon-helix-helix DNA-binding protein., Protein Sci 8(11):2494-500

 [2] Chivers PT., Sauer RT., 2000, Regulation of high affinity nickel uptake in bacteria. Ni2+-Dependent interaction of NikR with wild-type and mutant operator sites., J Biol Chem 275(26):19735-41

 [3] Krecisz S., Jones MD., Zamble DB., 2012, Nonspecific interactions between Escherichia coli NikR and DNA are critical for nickel-activated DNA binding., Biochemistry 51(40):7873-9

 [4] Schreiter ER, Sintchak MD, Guo Y, Chivers PT, Sauer RT, Drennan CL, 2003, Crystal structure of the nickel-responsive transcription factor NikR., Nat Struct Biol, 10(10):794 10.1038/nsb985

 [5] Schreiter ER, Wang SC, Zamble DB, Drennan CL, 2006, NikR-operator complex structure and the mechanism of repressor activation by metal ions., Proc Natl Acad Sci U S A, 103(37):13676 10.1073/pnas.0606247103

 [6] Phillips CM, Schreiter ER, Guo Y, Wang SC, Zamble DB, Drennan CL, 2008, Structural basis of the metal specificity for nickel regulatory protein NikR., Biochemistry, 47(7):1938 10.1021/bi702006h

 [7] Chivers PT, Sauer RT, 2002, NikR repressor: high-affinity nickel binding to the C-terminal domain regulates binding to operator DNA., Chem Biol, 9(10):1141 10.1016/s1074-5521(02)00241-7

 [8] Helmann JD, 2002, Sensing nickel. NikRs with two pockets., Chem Biol, 9(10):1055 10.1016/s1074-5521(02)00251-x

 [9] Leitch S, Bradley MJ, Rowe JL, Chivers PT, Maroney MJ, 2007, Nickel-specific response in the transcriptional regulator, Escherichia coli NikR., J Am Chem Soc, 129(16):5085 10.1021/ja068505y

 [10] Diederix RE, Fauquant C, Rodrigue A, Mandrand-Berthelot MA, Michaud-Soret I, 2008, Sub-micromolar affinity of Escherichia coli NikR for Ni(II)., Chem Commun (Camb), None(15):1813 10.1039/b719676h

 [11] Bloom SL, Zamble DB, 2004, Metal-selective DNA-binding response of Escherichia coli NikR., Biochemistry, 43(31):10029 10.1021/bi049404k

 [12] Carrington PE, Chivers PT, Al-Mjeni F, Sauer RT, Maroney MJ, 2003, Nickel coordination is regulated by the DNA-bound state of NikR., Nat Struct Biol, 10(2):126 10.1038/nsb890

 [13] Wang SC, Dias AV, Zamble DB, 2009, The "metallo-specific" response of proteins: a perspective based on the Escherichia coli transcriptional regulator NikR., Dalton Trans, None(14):2459 10.1039/b818167p

 [14] Wang SC, Li Y, Ho M, Bernal ME, Sydor AM, Kagzi WR, Zamble DB, 2010, The response of Escherichia coli NikR to nickel: a second nickel-binding site., Biochemistry, 49(31):6635 10.1021/bi100685k

 [15] Chivers PT, Tahirov TH, 2005, Structure of Pyrococcus horikoshii NikR: nickel sensing and implications for the regulation of DNA recognition., J Mol Biol, 348(3):597 10.1016/j.jmb.2005.03.017

 [16] Phillips CM, Nerenberg PS, Drennan CL, Stultz CM, 2009, Physical basis of metal-binding specificity in Escherichia coli NikR., J Am Chem Soc, 131(29):10220 10.1021/ja9026314

 [17] Wang SC, Li Y, Robinson CV, Zamble DB, 2010, Potassium is critical for the Ni(II)-responsive DNA-binding activity of Escherichia coli NikR., J Am Chem Soc, 132(5):1506 10.1021/ja909136h

 [18] Ha Y, Hu H, Higgins K, Maroney M, Hedman B, Hodgson K, Solomon E, 2019, The Electronic Structure of the Metal Active Site Determines the Geometric Structure and Function of the Metalloregulator NikR., Biochemistry, 58(34):3585 10.1021/acs.biochem.9b00542

 [19] Eitinger T., Mandrand-Berthelot MA., 2000, Nickel transport systems in microorganisms., Arch Microbiol 173(1):1-9

 [20] Dosanjh NS, Michel SL, 2006, Microbial nickel metalloregulation: NikRs for nickel ions., Curr Opin Chem Biol, 10(2):123 10.1016/j.cbpa.2006.02.011

 [21] Higgins KA, Carr CE, Maroney MJ, 2012, Specific metal recognition in nickel trafficking., Biochemistry, 51(40):7816 10.1021/bi300981m