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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 regulons Fis,MazE,MazE-MazF
Fis,MazE,MazE-MazF,ppGpp
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MazE-MazF,-](2)


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 -50.0 mazE, mazF, mazG
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE-MazF repressor mazEp1 nd -7.0 -36.0 mazE, mazF, mazG
tctacaatgtAGATTGATATATACTGTATCTACATATGatagcggttt
2911362 2911389 [BCE], [GEA], [SM] [1], [2]
  MazE-MazF repressor mazEp2 nd -34.0 -50.0 mazE, mazF, mazG
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE-MazF repressor mazEp2 nd -20.0 -36.0 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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