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AcrR DNA-binding transcriptional repressor

Synonyms: AcrR-Ethidium, AcrR-Proflavin, AcrR-R6G, AcrR
Summary:
The acriflavine resistance regulator , AcrR, regulates the expression of genes involved in multidrug transport and is classified in the nodulation-resistance division family |CITS: [8821940]|. It also acts as a global repressor for the mar-sox-rob regulon |CITS:[25176444]|.
The crystal structure of AcrR shows that this protein is folded into nine α-helices distributed in two domains: the DNA-binding domain, which forms the typical helix-turn-helix in the N-terminal domain, and the ligand-binding domain, which forms a large internal cavity for multidrug binding in the C-terminal domain |CITS: [17950313]|. Mutational analyses have been used to identify the critical role of some amino acids for AcrR activity, such as Glu-67 |CITS: [17950313]| and Arg-45 |CITS: [16189130]|.
The activity of AcrR, which belongs to the TetR family, appears to be regulated by ligands such as rhodamine 6G, ethidium, and proflavin |CITS: [17644067]|. When one of these ligands is bound to the C-terminal domain of AcrR, a conformational change in the N-terminal domain releases the regulator from its DNA-binding site. It has been suggested that the three AcrR ligands bind to distinct overlapping sites |CITS: [17950313]| and that two of them (ethidium and proflavin) can be simultaneously bound in the cavity |CITS: [17644067]|. This cavity has an inner surface with negative potential and the ligands are positively charged, thus favoring the binding between them |CITS: [17950313]|.
The acrR gene, whose expression is increased under general stress conditions |CITS: [8821940]|, is autoregulated and divergently transcribed from the acrAB operon.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
AcrR Functional   Apo [BPP], [IPI] [1], [2]
AcrR-Ethidium Non-Functional Allosteric Holo [BPP], [IPI] [1], [2]
AcrR-Proflavin Non-Functional Allosteric Holo [BPP], [IPI] [1], [2]
AcrR-R6G Non-Functional Allosteric Holo [BPP], [IPI] [1], [2]
Evolutionary Family: TetR/AcrR
Connectivity class: Local Regulator
Gene name: acrR
  Genome position: 485761-486408
  Length: 648 bp / 215 aa
Operon name: acrR
TU(s) encoding the TF:
Transcription unit        Promoter
acrR
acrRp


Regulon       
Regulated gene(s) acrA, acrB, acrR, marA, marB, marR, micF, soxR, soxS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
drug resistance/sensitivity (7)
Transcription related (5)
repressor (5)
operon (4)
detoxification (4)
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Regulated operon(s) acrAB, acrR, marRAB, micF, soxR, soxS
First gene in the operon(s) acrA, acrR, marR, micF, soxR, soxS
Simple and complex regulons AcrR
AcrR,CRP,CpxR,Cra,Fis,MarA,MarR,Rob,SoxS
AcrR,EnvR,MarA,MprA,PhoP,Rob,SoxS
AcrR,FNR,Fur,SoxR
AcrR,FNR,Fur,SoxR,SoxS
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[AcrR,-](6)


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
  AcrR repressor acrAp Sigma70 -22.5 -101.5 acrA, acrB
gcgttagattTACATACATTTGTGAATGTATGTAccatagcacg
485709 485732 [BCE], [BPP], [GEA], [HIBSCS] [2], [3], [4]
  AcrR repressor acrRp Sigma70 22.5 -40.5 acrR
cgtgctatggTACATACATTCACAAATGTATGTAaatctaacgc
485709 485732 [AIBSCS], [BCE], [BPP], [GEA], [HIBSCS] [2], [3], [4], [5]
  AcrR repressor marRp Sigma70 -40.5 -67.5 marR, marA, marB
catcggtcaaTTCATTCATTtgacttatac
1619048 1619057 [BPP], [GEA], [HIBSCS] [3]
  AcrR repressor micFp Sigma70 41.0 39.5 micF
atttattaccGTCATTCATTTCTGAATGTCTGTTtacccctatt
2313112 2313135 [AIBSCS] [5]
  AcrR repressor soxRp Sigma70 2.5 -20.5 soxR
ataattcctcAAGTTAACTTgaggtaaagc
4277444 4277453 [BPP], [GEA], [HIBSCS] [3]
  AcrR repressor soxSp Sigma70 -25.5 -65.5 soxS
gctttacctcAAGTTAACTTgaggaattat
4277444 4277453 [BPP], [GEA], [HIBSCS] [3]


Alignment and PSSM for AcrR TFBSs    

Aligned TFBS of AcrR   
  Sequence
  CATACATTTG
  CATTCATTTG
  CATTCATTTC
  AGTTAACTTG

Position weight matrix (PWM).   
A	1	3	0	1	1	4	0	0	0	0
C	3	0	0	0	3	0	1	0	0	1
G	0	1	0	0	0	0	0	0	0	3
T	0	0	4	3	0	0	3	4	4	0

PWM logo   


 


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


Evidence    

 [BPP] Binding of purified proteins

 [IPI] Inferred from physical interaction

 [BCE] Binding of cellular extracts

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [AIBSCS] Automated inference based on similarity to consensus sequences



Reference(s)    

 [1] Li M., Gu R., Su CC., Routh MD., Harris KC., Jewell ES., McDermott G., Yu EW., 2007, Crystal structure of the transcriptional regulator AcrR from Escherichia coli., J Mol Biol. 374(3):591-603

 [2] Su CC., Rutherford DJ., Yu EW., 2007, Characterization of the multidrug efflux regulator AcrR from Escherichia coli., Biochem Biophys Res Commun. 361(1):85-90

 [3] Lee JO., Cho KS., Kim OB., 2014, Overproduction of AcrR increases organic solvent tolerance mediated by modulation of SoxS regulon in Escherichia coli., Appl Microbiol Biotechnol. 98(20):8763-73

 [4] Ma D., Alberti M., Lynch C., Nikaido H., Hearst JE., 1996, The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals., Mol Microbiol. 19(1):101-12

 [5] Rodionov DA., Gelfand MS., Mironov AA., Rakhmaninova AB., 2001, Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria., J Mol Microbiol Biotechnol. 3(2):319-24



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