MQSA_ECOLI
ID MQSA_ECOLI Reviewed; 131 AA.
AC Q46864; Q2M9H9;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Antitoxin MqsA {ECO:0000303|PubMed:20041169};
GN Name=mqsA {ECO:0000303|PubMed:20041169}; Synonyms=ygiT;
GN OrderedLocusNames=b3021, JW2989;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [3]
RP IDENTIFICATION AS A TOXIN-ANTITOXIN SYSTEM, INDUCTION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=K12;
RX PubMed=16768798; DOI=10.1186/1471-2180-6-53;
RA Shah D., Zhang Z., Khodursky A., Kaldalu N., Kurg K., Lewis K.;
RT "Persisters: a distinct physiological state of E. coli.";
RL BMC Microbiol. 6:53-53(2006).
RN [4]
RP FUNCTION AS AN ANTITOXIN, FUNCTION AS A TRANSCRIPTIONAL REGULATOR, SUBUNIT,
RP DNA-BINDING, AND OPERON STRUCTURE.
RX PubMed=19690171; DOI=10.1074/jbc.m109.032904;
RA Yamaguchi Y., Park J.H., Inouye M.;
RT "MqsR, a crucial regulator for quorum sensing and biofilm formation, is a
RT GCU-specific mRNA interferase in Escherichia coli.";
RL J. Biol. Chem. 284:28746-28753(2009).
RN [5]
RP FUNCTION AS AN ANTITOXIN, DNA-BINDING, FUNCTION AS A TRANSCRIPTION
RP REGULATOR, INDUCTION, AND POSSIBLE CLEAVAGE BY CLPPX.
RC STRAIN=K12 / BW25113, and K12 / MG1655 / ATCC 47076;
RX PubMed=20105222; DOI=10.1111/j.1462-2920.2009.02147.x;
RA Kim Y., Wang X., Zhang X.S., Grigoriu S., Page R., Peti W., Wood T.K.;
RT "Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD.";
RL Environ. Microbiol. 12:1105-1121(2010).
RN [6]
RP FUNCTION AS AN MRNA INTERFERASE ANTITOXIN, INDUCTION, AND OPERON STRUCTURE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=19943910; DOI=10.1111/j.1365-2958.2009.06969.x;
RA Christensen-Dalsgaard M., Jorgensen M.G., Gerdes K.;
RT "Three new RelE-homologous mRNA interferases of Escherichia coli
RT differentially induced by environmental stresses.";
RL Mol. Microbiol. 75:333-348(2010).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, POSSIBLE CLEAVAGE BY LON, DNA-BINDING, AND
RP MUTAGENESIS OF 97-ASN--ARG-101.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=21516113; DOI=10.1038/nchembio.560;
RA Wang X., Kim Y., Hong S.H., Ma Q., Brown B.L., Pu M., Tarone A.M.,
RA Benedik M.J., Peti W., Page R., Wood T.K.;
RT "Antitoxin MqsA helps mediate the bacterial general stress response.";
RL Nat. Chem. Biol. 7:359-366(2011).
RN [8]
RP INDUCTION BY OTHER TA SYSTEMS.
RC STRAIN=K12 / BW25113;
RX PubMed=23432955; DOI=10.1186/1471-2180-13-45;
RA Kasari V., Mets T., Tenson T., Kaldalu N.;
RT "Transcriptional cross-activation between toxin-antitoxin systems of
RT Escherichia coli.";
RL BMC Microbiol. 13:45-45(2013).
RN [9]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, DNA-BINDING, AND MUTAGENESIS OF
RP ARG-61.
RX PubMed=23172222; DOI=10.1074/jbc.m112.421008;
RA Brown B.L., Lord D.M., Grigoriu S., Peti W., Page R.;
RT "The Escherichia coli toxin MqsR destabilizes the transcriptional
RT repression complex formed between the antitoxin MqsA and the mqsRA operon
RT promoter.";
RL J. Biol. Chem. 288:1286-1294(2013).
RN [10]
RP FUNCTION, AND DNA-BINDING.
RC STRAIN=K12 / BW25113;
RX PubMed=24212724; DOI=10.1038/srep03186;
RA Soo V.W., Wood T.K.;
RT "Antitoxin MqsA represses curli formation through the master biofilm
RT regulator CsgD.";
RL Sci. Rep. 3:3186-3186(2013).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / BW25113;
RX PubMed=25534751; DOI=10.1111/1462-2920.12749;
RA Kwan B.W., Lord D.M., Peti W., Page R., Benedik M.J., Wood T.K.;
RT "The MqsR/MqsA toxin/antitoxin system protects Escherichia coli during bile
RT acid stress.";
RL Environ. Microbiol. 17:3168-3181(2015).
RN [12]
RP PRELIMINARY CRYSTALLIZATION, COFACTOR, AND SUBUNIT.
RC STRAIN=K12;
RX PubMed=20823526; DOI=10.1107/s1744309110028617;
RA Brown B.L., Page R.;
RT "Preliminary crystallographic analysis of the Escherichia coli antitoxin
RT MqsA (YgiT/b3021) in complex with mqsRA promoter DNA.";
RL Acta Crystallogr. F 66:1060-1063(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ZINC AND MQSR,
RP SUBUNIT, DNA-BINDING, COFACTOR, AND DOMAIN.
RC STRAIN=K12;
RX PubMed=20041169; DOI=10.1371/journal.ppat.1000706;
RA Brown B.L., Grigoriu S., Kim Y., Arruda J.M., Davenport A., Wood T.K.,
RA Peti W., Page R.;
RT "Three dimensional structure of the MqsR:MqsA complex: a novel TA pair
RT comprised of a toxin homologous to RelE and an antitoxin with unique
RT properties.";
RL PLoS Pathog. 5:E1000706-E1000706(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH ZINC AND DNA,
RP COFACTOR, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ASN-97 AND ARG-101.
RC STRAIN=K12;
RX PubMed=21068382; DOI=10.1074/jbc.m110.172643;
RA Brown B.L., Wood T.K., Peti W., Page R.;
RT "Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its
RT gene promoter reveals extensive domain rearrangements and the specificity
RT of transcriptional regulation.";
RL J. Biol. Chem. 286:2285-2296(2011).
RN [15]
RP STRUCTURE BY NMR, COFACTOR, AND DOMAIN.
RX PubMed=22789559; DOI=10.1016/j.bbapap.2012.06.016;
RA Papadopoulos E., Collet J.F., Vukojevic V., Billeter M., Holmgren A.,
RA Graslund A., Vlamis-Gardikas A.;
RT "Solution structure and biophysical properties of MqsA, a Zn-containing
RT antitoxin from Escherichia coli.";
RL Biochim. Biophys. Acta 1824:1401-1408(2012).
CC -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system.
CC Labile antitoxin that binds to the MqsR mRNA interferase toxin and
CC neutralizes its endoribonuclease activity. Overexpression prevents
CC MqsR-mediated cessation of cell growth and inhibition of cell
CC proliferation. Initially reported to act as a cotranscription factor
CC with MqsA (PubMed:19690171, PubMed:20105222). Following further
CC experiments, the MqsR-MqsA complex does not bind DNA and all reported
CC data are actually due to a small fraction of free MqsA alone binding
CC DNA. Addition of MqsR to a preformed MqsA-promoter DNA complex causes
CC dissociation of the MqsA-DNA complex, probably causing derepression of
CC MqsA-repressed transcripts (PubMed:23172222). MqsA binds to 2
CC palindromes in the promoter region of the mqsRA operon activating its
CC transcription. Binds to other promoters, inducing mcbR and spy and
CC repressing cspD among others (PubMed:20105222). Binds to and represses
CC the rpoS promoter, the master stress regulator, resulting in decreased
CC cyclic-di-GMP, reduced stress resistance, increased cell motility and
CC decreased biofilm formation; in these experiments 5 TA systems are
CC missing (lacks MazEF, RelEB, ChpB, YoeB-YefM, YafQ-DinJ)
CC (PubMed:21516113). An earlier study showed overexpression alone
CC increases biofilm formation, perhaps by repressing cspD; in these
CC experiments the 5 TA systems are present (PubMed:20105222). Represses
CC the csgD promoter. In the presence of stress, when this protein is
CC degraded, the promoters it represses are derepressed, leading to
CC biofilm formation (Probable). This TA system mediates cell growth
CC during bile acid deoxycholate stress by degrading mRNA for probable
CC deoxycholate-binding protein YgiS; bile acid detergents such as
CC deoxycholate are important for host defense against bacterial growth in
CC the gall bladder and duodenum (PubMed:25534751).
CC {ECO:0000269|PubMed:19690171, ECO:0000269|PubMed:19943910,
CC ECO:0000269|PubMed:20105222, ECO:0000269|PubMed:21516113,
CC ECO:0000269|PubMed:23172222, ECO:0000269|PubMed:25534751,
CC ECO:0000303|PubMed:24212724}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20041169, ECO:0000269|PubMed:20823526,
CC ECO:0000269|PubMed:21068382, ECO:0000269|PubMed:22789559};
CC Note=Binds 1 Zn(2+) ion per subunit. {ECO:0000269|PubMed:20041169,
CC ECO:0000269|PubMed:20823526, ECO:0000269|PubMed:21068382,
CC ECO:0000269|PubMed:22789559};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC The MqsR-MqsA complex is exceptionally thermostable with a Tm of 83.4
CC degress Celsius versus 48.1 degress Celsius for MqsR and 61.1 degress
CC Celsius for MqsA. {ECO:0000269|PubMed:23172222};
CC -!- SUBUNIT: Homodimer. Crystallizes as a heterotetramer with MqsA, MqsR-
CC MqsA(2)-MqsR (PubMed:20041169). Purifies as a probable heterohexamer of
CC 2 MqsR dimers and 1 MqsA dimer (PubMed:19690171). Binds promoter DNA as
CC a dimer (PubMed:21068382). When the 2 dissociate the MsqR mRNA
CC interferase becomes active. {ECO:0000269|PubMed:19690171,
CC ECO:0000269|PubMed:20041169, ECO:0000269|PubMed:20823526,
CC ECO:0000269|PubMed:21068382}.
CC -!- INTERACTION:
CC Q46864; P69222: infA; NbExp=2; IntAct=EBI-1120353, EBI-1120746;
CC Q46864; P07000: pldB; NbExp=2; IntAct=EBI-1120353, EBI-9134416;
CC Q46864; P0ACQ0: rbsR; NbExp=3; IntAct=EBI-1120353, EBI-1119646;
CC Q46864; P0A7L8: rpmA; NbExp=2; IntAct=EBI-1120353, EBI-546875;
CC Q46864; P0AGB6: rpoE; NbExp=2; IntAct=EBI-1120353, EBI-1129580;
CC Q46864; P0AAU7: ybfE; NbExp=2; IntAct=EBI-1120353, EBI-9138393;
CC -!- INDUCTION: Induced by amino acid starvation, glucose starvation and
CC when translation is blocked. Induction is decreased in the absence of
CC the Lon protease suggesting, by homology to other toxin-antitoxin
CC systems, that Lon may degrade the MqsA antitoxin. Transcription is
CC activated by MqsA (PubMed:20105222). It has been suggested that MqsA
CC represses its own operon (PubMed:19690171). Not more induced in
CC persister cells (PubMed:16768798). A member of the mqsRA operon. This
CC operon induced by ectopic expression of toxins RelE, HicA and YafQ but
CC not by MazF or HicA (PubMed:23432955). {ECO:0000269|PubMed:16768798,
CC ECO:0000269|PubMed:19943910, ECO:0000269|PubMed:20105222,
CC ECO:0000269|PubMed:23432955, ECO:0000303|PubMed:19690171}.
CC -!- DOMAIN: The Zn-binding N-terminal domain (residues 1-65) binds to the
CC MqsR mRNA interferase toxin and makes contact with the DNA phosphate
CC backbone, while the C-terminus (residues 70-131) binds the promoter in
CC a sequence-specific manner. They are linked by a short flexible domain
CC (PubMed:22789559). {ECO:0000269|PubMed:20041169,
CC ECO:0000269|PubMed:21068382, ECO:0000269|PubMed:22789559}.
CC -!- PTM: Degraded in the presence of oxidative stress, maybe by the Lon
CC and/or ClpX proteases. {ECO:0000303|PubMed:20105222,
CC ECO:0000303|PubMed:21516113}.
CC -!- DISRUPTION PHENOTYPE: Essential for growth, it cannot be disrupted
CC (PubMed:16768798). A double mqsR-mqsA deletion leads to increased rpoS
CC mRNA levels, resulting in increased cyclic-di-GMP levels, increasing
CC stress resistance, increased biofilm formation (PubMed:21516113). The
CC double mutant has increased metabolism and respiration in the presence
CC of the bile acid deoxycholate and consequently grows less well.
CC Decreases cell survival in the presence of 20% deoxycholate
CC (PubMed:25534751). {ECO:0000269|PubMed:16768798,
CC ECO:0000269|PubMed:21516113, ECO:0000269|PubMed:25534751}.
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DR EMBL; U28377; AAA69189.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76057.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77077.1; -; Genomic_DNA.
DR PIR; C65089; C65089.
DR RefSeq; NP_417493.1; NC_000913.3.
DR RefSeq; WP_000650107.1; NZ_STEB01000001.1.
DR PDB; 2KZ8; NMR; -; A=1-131.
DR PDB; 3FMY; X-ray; 1.40 A; A=62-131.
DR PDB; 3GA8; X-ray; 1.70 A; A=1-76.
DR PDB; 3GN5; X-ray; 2.15 A; A/B=1-131.
DR PDB; 3HI2; X-ray; 2.00 A; A/C=1-76.
DR PDB; 3O9X; X-ray; 2.10 A; A/B=1-131.
DR PDBsum; 2KZ8; -.
DR PDBsum; 3FMY; -.
DR PDBsum; 3GA8; -.
DR PDBsum; 3GN5; -.
DR PDBsum; 3HI2; -.
DR PDBsum; 3O9X; -.
DR AlphaFoldDB; Q46864; -.
DR BMRB; Q46864; -.
DR SMR; Q46864; -.
DR BioGRID; 4259247; 153.
DR BioGRID; 850181; 51.
DR ComplexPortal; CPX-1084; MqsRA toxin-antitoxin complex.
DR DIP; DIP-12226N; -.
DR IntAct; Q46864; 54.
DR STRING; 511145.b3021; -.
DR jPOST; Q46864; -.
DR PaxDb; Q46864; -.
DR PRIDE; Q46864; -.
DR EnsemblBacteria; AAC76057; AAC76057; b3021.
DR EnsemblBacteria; BAE77077; BAE77077; BAE77077.
DR GeneID; 945814; -.
DR KEGG; ecj:JW2989; -.
DR KEGG; eco:b3021; -.
DR PATRIC; fig|1411691.4.peg.3709; -.
DR EchoBASE; EB2840; -.
DR eggNOG; COG2944; Bacteria.
DR HOGENOM; CLU_115776_1_1_6; -.
DR OMA; CGEGIWD; -.
DR BioCyc; EcoCyc:G7571-MON; -.
DR BioCyc; MetaCyc:G7571-MON; -.
DR EvolutionaryTrace; Q46864; -.
DR PRO; PR:Q46864; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:EcoCyc.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:EcoCyc.
DR GO; GO:0044010; P:single-species biofilm formation; IDA:ComplexPortal.
DR CDD; cd00093; HTH_XRE; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR InterPro; IPR022452; MqsA.
DR InterPro; IPR032758; MqsA/HigA-2.
DR InterPro; IPR022453; Znf_MqsA-type.
DR Pfam; PF15731; MqsA_antitoxin; 1.
DR SMART; SM00530; HTH_XRE; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR TIGRFAMs; TIGR03830; CxxCG_CxxCG_HTH; 1.
DR TIGRFAMs; TIGR03831; YgiT_finger; 1.
DR PROSITE; PS50943; HTH_CROC1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Metal-binding; Reference proteome; Repressor;
KW Stress response; Toxin-antitoxin system; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..131
FT /note="Antitoxin MqsA"
FT /id="PRO_0000149762"
FT DOMAIN 74..127
FT /note="HTH cro/C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT DNA_BIND 85..104
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT BINDING 3
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20041169,
FT ECO:0000269|PubMed:20823526, ECO:0000269|PubMed:21068382,
FT ECO:0000269|PubMed:22789559"
FT BINDING 6
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20041169,
FT ECO:0000269|PubMed:20823526, ECO:0000269|PubMed:21068382,
FT ECO:0000269|PubMed:22789559"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20041169,
FT ECO:0000269|PubMed:20823526, ECO:0000269|PubMed:21068382,
FT ECO:0000269|PubMed:22789559"
FT BINDING 40
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20041169,
FT ECO:0000269|PubMed:20823526, ECO:0000269|PubMed:21068382,
FT ECO:0000269|PubMed:22789559"
FT MUTAGEN 61
FT /note="R->A,D: Decreases DNA-binding, decreases
FT thermostability of MqsR-MqsA complex."
FT /evidence="ECO:0000269|PubMed:23172222"
FT MUTAGEN 97..101
FT /note="NAFSR->AAFSA: Abolishes DNA-binding, including
FT binding to the rpoS promoter."
FT /evidence="ECO:0000269|PubMed:21068382,
FT ECO:0000269|PubMed:21516113"
FT MUTAGEN 97
FT /note="N->A: 50-fold reduction in DNA-binding."
FT /evidence="ECO:0000269|PubMed:21068382"
FT MUTAGEN 101
FT /note="R->A: 10-fold reduction in DNA-binding."
FT /evidence="ECO:0000269|PubMed:21068382"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:3GA8"
FT STRAND 7..22
FT /evidence="ECO:0007829|PDB:3GA8"
FT STRAND 25..37
FT /evidence="ECO:0007829|PDB:3GA8"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:3GA8"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:3HI2"
FT HELIX 47..66
FT /evidence="ECO:0007829|PDB:3GA8"
FT HELIX 71..80
FT /evidence="ECO:0007829|PDB:3FMY"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:3FMY"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:3FMY"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:3FMY"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:3FMY"
FT HELIX 127..130
FT /evidence="ECO:0007829|PDB:3FMY"
SQ SEQUENCE 131 AA; 14703 MW; AA26A2793AD84447 CRC64;
MKCPVCHQGE MVSGIKDIPY TFRGRKTVLK GIHGLYCVHC EESIMNKEES DAFMAQVKAF
RASVNAETVA PEFIVKVRKK LSLTQKEASE IFGGGVNAFS RYEKGNAQPH PSTIKLLRVL
DKHPELLNEI R
