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NikR DNA-binding transcriptional repressor

Synonyms: NikR-Ni2+, NikR-Cd2+, NikR-Co2+, NikR-Cu+, NikR-Zn2+, NikR
Summary:
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 [2]. 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 [3]. The two RHH DNA-binding domains flank the tetrameric core of the protein []. 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]. 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 [].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NikR Non-Functional   Apo nd nd
NikR-Cd2+ Functional Allosteric Holo nd nd
NikR-Co2+ Functional Allosteric Holo nd nd
NikR-Cu+ Functional Allosteric Holo nd nd
NikR-Ni2+ Functional Allosteric Holo [APPH], [IPI] [1], [2]
NikR-Zn2+ Functional Allosteric Holo nd nd
Evolutionary Family: CopG
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
nikABCDER
nikAp1
nikABCDER
nikAp2
nikR
nikRp


Regulon       
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)
[NikR,-](1)


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 (Confirmed, Strong, Weak) References
  NikR-Ni2+ repressor nikAp1 nd -12.5 -51.0 nikA, nikB, nikC, nikD, nikE, nikR
caggtaatcaGTATGACGAATACTTAAAATCGTCATACttatttccgc
3613602 3613630 [BPP] [1], [3], [4]


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


Evidence    

 [APPH] Assay of protein purified to homogeneity

 [IPI] Inferred from physical interaction

 [BPP] Binding of purified proteins



Reference(s)    

 [1] 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

 [2] 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):794-9

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

 [4] 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

 [5] 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) (15):1813-5

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



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