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MazE-MazF DNA-binding transcriptional repressor

Synonyms: MazE-MazF
Summary:
MazF is a toxin that is counteracted by the MazE antitoxin [3]. The mazEF system causes a "programmed cell death" response to stresses including starvation [3] and antibiotics [4]. The antitoxin, MazE, is subject to degradation by ClpP-ClpA protease complex and exhibits a short (30 minute) half life, whereas the toxin, MazF, is much more stable [3]. The structure of the MazE-MazF complex is presented at 1.7 A resolution [5]. The complex is hexameric and is comprised of a MazE homodimer sandwiched between MazF homodimers [5]. It has been shown that the C terminus of the MazE TF plays an important role for MazE by increasing its binding affinity for the palindromic single-site operator [6] Review: [7, 8]. Read more >


Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MazE-MazF Functional   [IE] nd
Connectivity class: Local Regulator
Gene name: mazE
  Genome position: 2911091-2911339
  Length: 249 bp / 82 aa
Operon name: relA-mazEFG
TU(s) encoding the TF:
Transcription unit        Promoter
mazEFG
mazEp1
mazEFG
mazEp2
relA-mazEF
relAp1
relA-mazEF
relAp2
Gene name: mazF
  Genome position: 2910756-2911091
  Length: 336 bp / 111 aa
Operon name: relA-mazEFG
TU(s) encoding the TF:
Transcription unit        Promoter
mazEFG
mazEp1
mazEFG
mazEp2
relA-mazEF
relAp1
relA-mazEF
relAp2


Regulon       
Regulated gene(s) mazE, mazF, mazG
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
starvation (3)
defense/survival (2)
other (mechanical, nutritional, oxidative stress) (2)
cell killing (2)
drug resistance/sensitivity (2)
Read more >
Regulated operon(s) relA-mazEFG
First gene in the operon(s) mazE, mazE
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
  MazE-MazF repressor mazEp1 nd -21.0 -50.5 mazE, mazF, mazG
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE-MazF repressor mazEp1 nd -7.0 -36.5 mazE, mazF, mazG
tctacaatgtAGATTGATATATACTGTATCTACATATGatagcggttt
2911362 2911389 [BCE], [GEA], [SM] [1], [2]
  MazE-MazF repressor mazEp2 nd -34.0 -50.5 mazE, mazF, mazG
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE-MazF repressor mazEp2 nd -20.0 -36.5 mazE, mazF, mazG
tctacaatgtAGATTGATATATACTGTATCTACATATGatagcggttt
2911362 2911389 [BCE], [GEA], [SM] [1], [2]


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


Evidence    

 [IE] Inferred from experiment

 [BCE] Binding of cellular extracts

 [GEA] Gene expression analysis

 [SM] Site mutation



Reference(s)    

 [1] Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G., 2001, The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome., J Biol Chem 276(8):5975-84

 [2] Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E., 1993, chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100., J Bacteriol 175(21):6850-6

 [3] Aizenman E., Engelberg-Kulka H., Glaser G., 1996, An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death., Proc Natl Acad Sci U S A 93(12):6059-63

 [4] Sat B, Hazan R, Fisher T, Khaner H, Glaser G, Engelberg-Kulka H, 2001, Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality., J Bacteriol, 2001 Mar

 [5] Kamada K, Hanaoka F, Burley SK, 2003, Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition., Mol Cell, 2003 Apr

 [6] Zorzini V, Buts L, Schrank E, Sterckx YG, Respondek M, Engelberg-Kulka H, Loris R, Zangger K, van Nuland NA, 2015, Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding., Nucleic Acids Res, 2015 Jan

 [7] de la Cueva-Méndez G, 2003, Distressing bacteria: structure of a prokaryotic detox program., Mol Cell, 2003 Apr

 [8] Yamaguchi Y, Inouye M, 2011, Regulation of growth and death in Escherichia coli by toxin-antitoxin systems., Nat Rev Microbiol, 2011 Sep 19



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