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RelB-RelE DNA-binding transcriptional repressor

Synonyms: RelB-RelE
Summary:
RelB is a DNA-binding transcriptional regulator which belongs to the ribbon-helix-helix (RHH) family of transcription factors [1, 3, 4]and it is an antitoxin that prevents the lethal action of the toxin [5] RelB is part of the relBE-hokD operon, which specifies a toxin-antitoxin system, and it is autoregulated by its own products, RelB and RelE [1, 5, 6] On the other hand, relE encodes a cytotoxin that is lethal or inhibitory to host cells [5] and it also encodes a cofactor that enhances the repressor activity of RelB [1, 5, 6] The relBE-hokD operon is induced upon entering nutritional starvation conditions, such as the stringent response or acid starvation [7, 8] while the level of RelB antitoxin is reduced as a result of Lon-dependent proteolysis.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
RelB-RelE Functional   [APPHINH], [ICWHO], [IEP] [1]
Connectivity class: Local Regulator
Gene name: relB
  Genome position: 1645633-1645872
  Length: 240 bp / 79 aa
Operon name: relBE-hokD
TU(s) encoding the TF:
Transcription unit        Promoter
relBE-hokD
relBp
null
null
Gene name: relE
  Genome position: 1645346-1645633
  Length: 288 bp / 95 aa
Operon name: relBE-hokD
TU(s) encoding the TF:
Transcription unit        Promoter
relBE-hokD
relBp
null
null


Regulon       
Regulated gene(s) hokD, relB, relE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
RNA degradation (2)
translation attenuation and efficiency (2)
cell killing (2)
prophage genes and phage related functions (1)
Transcription related (1)
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Regulated operon(s) relBE-hokD
First gene in the operon(s) relB
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 (Confirmed, Strong, Weak) References
  RelB-RelE repressor relBp Sigma70 -13.5 -44.5 relB, relE, hokD
cctaagcatgTTGTAGTGCGATacttgtaatg
1645911 1645922 [BPP], [GEA], [HIBSCS] [1]
  RelB-RelE repressor relBp Sigma70 1.5 -30.5 relB, relE, hokD
agtgcgatacTTGTAATGACATttgtaattac
1645897 1645908 [BPP], [GEA], [HIBSCS], [SM] [1], [2]
  RelB-RelE repressor relBp Sigma70 13.5 -19.0 relB, relE, hokD
tgtaatgacaTTTGTAATTACAAgaggtgtaag
1645885 1645897 [BPP], [HIBSCS] [1]
  RelB-RelE repressor relBp Sigma70 28.0 -4.5 relB, relE, hokD
aattacaagaGGTGTAAGACATgggtagcatt
1645871 1645882 [BPP], [GEA], [HIBSCS] [1]


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


Evidence    

 [APPHINH] Assay of protein purified to homogeneity from its native host

 [ICWHO] Inferred computationally without human oversight

 [IEP] Inferred from expression pattern

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation



Reference(s)    

 [1] Li GY., Zhang Y., Inouye M., Ikura M., 2008, Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module., J Mol Biol 380(1):107-19

 [2] Belliveau NM., Barnes SL., Ireland WT., Jones DL., Sweredoski MJ., Moradian A., Hess S., Kinney JB., Phillips R., 2018, Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria., Proc Natl Acad Sci U S A 115(21):E4796-E4805

 [3] Anantharaman V, Aravind L, 2003, New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system., Genome Biol, 2003

 [4] Cherny I, Overgaard M, Borch J, Bram Y, Gerdes K, Gazit E, 2007, Structural and thermodynamic characterization of the Escherichia coli RelBE toxin-antitoxin system: indication for a functional role of differential stability., Biochemistry, 2007 Oct 30

 [5] Gotfredsen M, Gerdes K, 1998, The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family., Mol Microbiol, 1998 Aug

 [6] Galvani C, Terry J, Ishiguro EE, 2001, Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes., J Bacteriol, 2001 Apr

 [7] Christensen SK, Mikkelsen M, Pedersen K, Gerdes K, 2001, RelE, a global inhibitor of translation, is activated during nutritional stress., Proc Natl Acad Sci U S A, 2001 Dec 4

 [8] Pistolese GR, Ippoliti A, Mauriello A, Pistolese C, Pocek M, Simonetti G, 2002, Postoperative regression of retroperitoneal fibrosis in patients with inflammatory abdominal aortic aneurysms: evaluation with spiral computed tomography., Ann Vasc Surg, 2002 Mar

 [9] Grady R, Hayes F, 2003, Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium., Mol Microbiol, 2003 Mar

 [10] Overgaard M, Borch J, Jørgensen MG, Gerdes K, 2008, Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity., Mol Microbiol, 2008 Aug

 [11] Overgaard M, Borch J, Gerdes K, 2009, RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB., J Mol Biol, 2009 Nov 27

 [12] Li GY, Zhang Y, Inouye M, Ikura M, 2009, Inhibitory mechanism of Escherichia coli RelE-RelB toxin-antitoxin module involves a helix displacement near an mRNA interferase active site., J Biol Chem, 2009 May 22

 [13] Takagi H, Kakuta Y, Okada T, Yao M, Tanaka I, Kimura M, 2005, Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects., Nat Struct Mol Biol, 2005 Apr

 [14] Gerdes K, 2000, Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress., J Bacteriol, 2000 Feb

 [15] Lavallé R, 1965, [New mutants for regulation of RNA synthesis]., Bull Soc Chim Biol (Paris), 1965

 [16] Diderichsen B, Fiil NP, Lavallé R, 1977, Genetics of the relB locus in Escherichia coli., J Bacteriol, 1977 Jul

 [17] Bech FW., Jorgensen ST., Diderichsen B., Karlstrom OH., 1985, Sequence of the relB transcription unit from Escherichia coli and identification of the relB gene., EMBO J 4(4):1059-66

 [18] Wilson DN, Nierhaus KH, 2005, RelBE or not to be., Nat Struct Mol Biol, 2005 Apr



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