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MqsA DNA-binding transcriptional repressor

Synonyms: MqsA
Summary:
The antitoxin MqsA belongs to the toxin-antitoxin system MqsR-MqsA, which controls biofilm formation and triggers programmed cell death in E. coli [3]. mqsR is cotranscribed with the downstream gene mqsA, and their respective open reading frames are separated by 1 bp.
The toxin MqsR functions as an mRNA interferase, that is, it possesses endoribonuclease activity and cleaves mRNA at the specific sequence GCU, 5' or 3' of the G. Elevated levels of free MqsR result in programmed cell death due to the degradation of mRNA and concomitant inhibition of protein synthesis [3].
The antitoxin MqsA has two functions. It binds and thereby inhibits the endoribonuclease activity of MqsR. In addition it is a DNA-binding protein, as is the case for other bacterial antitoxins. MqsA recognizes two palindromic sites located between the promoter and the start codon of mqsR. Binding to these sites is enhanced when MqsA is bound to MqsR. Therefore, it has been suggested that MqsA and the MqsA-MqsR complex negatively autoregulate expression of the mqsRA operon [3].
Solution [5, 6] and crystal structures [7, 8] of MqsA have been solved.
Both MqsR and MqsA are dimeric proteins.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MqsA     nd nd
Evolutionary Family: CxxCG_CxxCG_HTH, MqsR
Connectivity class: Local Regulator
Gene name: mqsA
  Genome position: 3167851-3168246
  Length: 396 bp / 131 aa
Operon name: mqsRA
TU(s) encoding the TF:
Transcription unit        Promoter
mqsRA
mqsRp
mqsRA
mqsRp2
Gene name: mqsR
  Genome position: 3168248-3168544
  Length: 297 bp / 98 aa
Operon name: mqsRA
TU(s) encoding the TF:
Transcription unit        Promoter
mqsRA
mqsRp
mqsRA
mqsRp2


Regulon       
Regulated gene(s) csgD, csgE, csgF, csgG, cspD, mqsA, mqsR, rpoS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
Transcription related (1)
activator (1)
repressor (1)
Accessory Factors Involved in Transport (1)
Putative uncharacterized transport protein (1)
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Regulated operon(s) csgDEFG, cspD, mqsRA, nlpD-rpoS
First gene in the operon(s) csgD, cspD, mqsR, rpoS
Simple and complex regulons ArcA,CRP,Fur,GadX,MqsA
BasR,CRP,CpxR,Cra,CsgD,FliZ,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA
CRP,H-NS,MqsA
MqsA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MqsA,-](4)


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
  MqsA repressor csgDp1 Sigma38 -83.5 -231.0 csgD, csgE, csgF, csgG
aacttaataaAACCTTAAGGTTAacattttaat
1103421 1103433 [BPP], [GEA], [HIBSCS] [1]
  MqsA repressor cspDp Sigma70 -132.5 -218.5 cspD
tgatagataaCTATCATCTATCGTTGGCatcagcgaca
922800 922817 [BPP], [GEA] [2]
  MqsA repressor cspDp Sigma70 101.5 14.5 cspD
aagcatggaaAAGGGTACTGTTAAGTGGttcaacaatg
922567 922584 [BPP], [GEA] [2]
  MqsA repressor mqsRp Sigma70 42.0 -68.0 mqsR, mqsA
tacatctaacTAACCTTTTAGGTGCtttttcattg
3168605 3168619 [BPP], [HIBSCS], [IHBCE] [3]
  MqsA repressor mqsRp Sigma70 74.0 -36.0 mqsR, mqsA
ttgctgtaatTAACCTTTTAGGTTAtaactaaagt
3168573 3168587 [BPP], [HIBSCS], [IHBCE] [3]
  MqsA repressor rpoSp Sigma70 -147.0 -714.0 rpoS
aacgttggtcAGACCTTGCAGGTGGgtaatgcttc
2868258 2868272 [BPP], [GEA], [IHBCE], [SM] [4]


Alignment and PSSM for MqsA TFBSs    

Aligned TFBS of MqsA   
  Sequence
  ACTGTTAAGTGGTT
  AACGATAGATGATA
  CCTTGCAGGTGGGT
  CCTTTTAGGTTATA
  CCTTTTAGGTGCTT

Position weight matrix (PWM).   
A	2	1	0	0	1	0	5	1	1	0	0	2	0	2
C	3	4	1	0	0	1	0	0	0	0	0	1	0	0
G	0	0	0	2	1	0	0	4	4	0	4	2	1	0
T	0	0	4	3	3	4	0	0	0	5	1	0	4	3

PWM logo   


 


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


Evidence    

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [IHBCE] Inferred by a human based on computational evidence

 [SM] Site mutation



Reference(s)    

 [1] Soo VW., Wood TK., 2013, Antitoxin MqsA represses curli formation through the master biofilm regulator CsgD., Sci Rep. 3:3186

 [2] Kim Y., Wang X., Zhang XS., Grigoriu S., Page R., Peti W., Wood TK., 2010, Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD., Environ Microbiol. 12(5):1105-21

 [3] Yamaguchi Y., Park JH., Inouye M., 2009, MqsR, a crucial regulator for quorum sensing and biofilm formation, is a GCU-specific mRNA interferase in Escherichia coli., J Biol Chem. 284(42):28746-53

 [4] Wang X., Kim Y., Hong SH., Ma Q., Brown BL., Pu M., Tarone AM., Benedik MJ., Peti W., Page R., Wood TK., 2011, Antitoxin MqsA helps mediate the bacterial general stress response., Nat Chem Biol. 7(6):359-66

 [5] Papadopoulos E., Billeter M., Graslund A., Vlamis-Gardikas A., 2007, Assignment of (1)H, (13)C, and (15)N resonances of YgiT, a putative DNA interacting protein from E. coli, containing one HTH and two CxxC motifs., Biomol NMR Assign. 1(2):217-9

 [6] Papadopoulos E., Collet JF., Vukojevic V., Billeter M., Holmgren A., Graslund A., Vlamis-Gardikas A., 2012, Solution structure and biophysical properties of MqsA, a Zn-containing antitoxin from Escherichia coli., Biochim Biophys Acta. 1824(12):1401-8

 [7] Brown BL., Grigoriu S., Kim Y., Arruda JM., Davenport A., Wood TK., Peti W., Page R., 2009, Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties., PLoS Pathog. 5(12):e1000706

 [8] Brown BL., Wood TK., Peti W., Page R., 2011, Structure of the Escherichia coli Antitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation., J Biol Chem. 286(3):2285-96

 [9] Yamaguchi Y., Park JH., Inouye M., 2011, Toxin-antitoxin systems in bacteria and archaea., Annu Rev Genet. 45:61-79

 [10] Yamaguchi Y., Inouye M., 2009, mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems., Prog Mol Biol Transl Sci. 85:467-500

 [11] Inouye M., 2006, The discovery of mRNA interferases: implication in bacterial physiology and application to biotechnology., J Cell Physiol. 209(3):670-6



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