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YefM-YoeB DNA-binding transcriptional repressor

Synonyms: YefM-YoeB
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, 3] The yefM gene is upregulated during growth in biofilms [4]and yefM-yoeB is upregulated in persister cells [5] 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 [3] 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 [3] The palindrome L covers the whole -10 box and the S palindrome surrounds the transcription start site; because of these placements, the YoeB-YefM complex specifically represses the transcription of the system by blocking RNA polymerase binding [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] The -35 region of the yefM-yoeB promoter does not have the conserved motif of σ70 promoters, and this results in a low transcriptional activity relative to that of other toxin-antitoxin operons with the cognate motif (i.e., axe-txe) [2]. The sequences of the core repressor binding sites of homologous toxin-antitoxin systems can be nearly identical; however, they can be differently positioned in relation to the main promoter elements, resulting in important differences in the level of transcription repression [2]. YefM originally was described as a native unstructured protein [6] later it was reevaluated as experimental, and modeling data have demonstrated that the protein is at least partially folded [1, 7]and dimeric [1] The YefM antitoxin forms a heterotrimeric complex with the YoeB toxin (YefM2-YoeB) [8, 9] The tertiary structure of the YoeB toxin and the YefM2-YoeB complex has been described [9] 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-YoeB Functional   nd nd
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
yefM-yoeB
yefMp
Gene name: yoeB
  Genome position: 2089211-2089465
  Length: 255 bp / 84 aa
Operon name: yefM-yoeB
TU(s) encoding the TF:
Transcription unit        Promoter
yefM-yoeB
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,YefM-YoeB
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
  YefM-YoeB repressor yefMp Sigma70 -10.5 -30.5 yefM, yoeB
ttaacgctcaTCATTGTACAATGAactgtacaaa
2089737 2089750 [GEA], [APIORCISFBSCS], [BPP] [1], [2]
  YefM-YoeB repressor yefMp Sigma70 2.5 -18.5 yefM, yoeB
attgtacaatGAACTGTACAAAAGaggagattga
2089725 2089738 [GEA], [APIORCISFBSCS], [BCE], [BPP] [1], [2]


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




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] Kedzierska B., Potrykus K., Szalewska-Palasz A., Wodzikowska B., 2020, Insights into Transcriptional Repression of the Homologous Toxin-Antitoxin Cassettes yefM-yoeB and axe-txe., Int J Mol Sci 21(23)

 [3] Bailey SE, Hayes F, 2009, Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex., J Bacteriol, 191(3):762 10.1128/JB.01331-08

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

 [5] Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K, 2006, Persisters: a distinct physiological state of E. coli., BMC Microbiol, 6(None):53 10.1186/1471-2180-6-53

 [6] Cherny I, Gazit E, 2004, The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target., J Biol Chem, 279(9):8252 10.1074/jbc.M308263200

 [7] 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, 46(3):210 10.1006/plas.2001.1548

 [8] 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, 280(34):30063 10.1074/jbc.M506220200

 [9] Kamada K, Hanaoka F, 2005, Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin., Mol Cell, 19(4):497 10.1016/j.molcel.2005.07.004

 [10] 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, 47(5):1419 10.1046/j.1365-2958.2003.03387.x



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