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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, 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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
YefM Functional   nd nd nd
Evolutionary Family: YefM, YoeB/Txe_like
TFBs length: 14
TFBs symmetry: inverted-repeat
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


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)
[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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  YefM repressor yefMp Sigma70 -10.5 -30.5 yefM, yoeB
attaacgctcATCATTGTACAATGAactgtacaaa
2089737 2089751 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] W [1]
  YefM repressor yefMp Sigma70 2.5 -18.5 yefM, yoeB
cattgtacaaTGAACTGTACAAAAGaggagattga
2089725 2089739 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [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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