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YefM DNA-binding transcriptional repressor

Synonyms: YefM
Summary:
YefM is a transcriptional DNA-binding autorepressor for the yefM-yoeB operon. In addition, YefM also functions as an antitoxin to form a complex with YoeB, which is a toxin that is counteracted by YefM antitoxin [1] YefM can bind alone with low affinity to the yefM-yoeB operator, but together with YoeB it has an enhanced DNA-binding affinity compared to free YefM [1] YoeB enhances the interaction with YefM by affecting the YefM conformation to one that is more favorable for DNA binding and/or by stabilizing the nucleoprotein complex at the operator site and reducing basal expression of the yefM-yoeB operon [1, 2] The yefM gene is upregulated during growth in biofilms [3]and yefM-yoeB is upregulated in persister cells [4] it is probable that derepression of yefM-yoeB autoregulation occurs in these circumstances in response to an as-yet-unknown environmental or cell cycle signal(s) that interferes with the YefM-YoeB-operator interaction [2] The operator site 5' of yefM-yoeB comprises adjacent long (L) and short (S) palindromes with core 5'-TGTACA-3' motifs with a center-to-center distance of 12 bp [1] which was suggested to be crucial for the correct stable positioning of YefM-YoeB at the two repeats [2] This sequence organization is common in yefM-yoeB regulatory regions in diverse genomes, suggesting that interaction of YefM-YoeB with these motifs is a conserved mechanism of operon autoregulation [1] Nevertheless, YefM originally was described as a native unstructured protein [5] later it was reevaluated as experimental, and modeling data have demonstrated that the protein is at least partially folded [1, 6]and dimeric [1] The YefM antitoxin forms a heterotrimeric complex with the YoeB toxin (YefM2-YoeB) [7, 8] The tertiary structure of the YoeB toxin and the YefM2-YoeB complex has been described [8] In the complex, one C terminus in the YefM homodimer is unfolded and the other one shows an α-helical conformation and conceals the endoribonuclease fold of YoeB.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
YefM Functional   [APPH] [1]
Evolutionary Family: YefM, YoeB/Txe_like
Connectivity class: Local Regulator
Gene name: yefM
  Genome position: 2089462-2089713
  Length: 252 bp / 83 aa
Operon name: yefM-yoeB
TU(s) encoding the TF:
Transcription unit        Promoter
null
yefMp


Regulon       
Regulated gene(s) yefM, yoeB
Multifun term(s) of regulated gene(s)
defense/survival (2)
Regulated operon(s) yefM-yoeB
First gene in the operon(s) yefM
Simple and complex regulons YefM
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[YefM,-](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
  YefM repressor yefMp Sigma70 -10.5 -31.0 yefM, yoeB
attaacgctcATCATTGTACAATGAactgtacaaa
2089737 2089751 [BPP], [GEA], [HIBSCS] [1]
  YefM repressor yefMp Sigma70 2.5 -19.0 yefM, yoeB
cattgtacaaTGAACTGTACAAAAGaggagattga
2089725 2089739 [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    

 [APPH] Assay of protein purified to homogeneity

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences



Reference(s)    

 [1] Kedzierska B., Lian LY., Hayes F., 2007, Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression., Nucleic Acids Res 35(1):325-39

 [2] Bailey SE, Hayes F, 2009, Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex., J Bacteriol, 2009 Feb

 [3] Ren D., Bedzyk LA., Thomas SM., Ye RW., Wood TK., 2004, Gene expression in Escherichia coli biofilms., Appl Microbiol Biotechnol 64(4):515-24

 [4] Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K, 2006, Persisters: a distinct physiological state of E. coli., BMC Microbiol, 2006 Jun 12

 [5] Cherny I, Gazit E, 2004, The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target., J Biol Chem, 2004 Feb 27

 [6] Pomerantsev AP, Golovliov IR, Ohara Y, Mokrievich AN, Obuchi M, Norqvist A, Kuoppa K, Pavlov VM, 2001, Genetic organization of the Francisella plasmid pFNL10., Plasmid, 2001 Nov

 [7] Cherny I, Rockah L, Gazit E, 2005, The YoeB toxin is a folded protein that forms a physical complex with the unfolded YefM antitoxin. Implications for a structural-based differential stability of toxin-antitoxin systems., J Biol Chem, 2005 Aug 26

 [8] Kamada K, Hanaoka F, 2005, Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin., Mol Cell, 2005 Aug 19

 [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



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