MAZE_ECOLI
ID MAZE_ECOLI Reviewed; 82 AA.
AC P0AE72; P18534; Q2MA49;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Antitoxin MazE;
GN Name=mazE; Synonyms=chpAI, chpR; OrderedLocusNames=b2783, JW2754;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND OPERON STRUCTURE.
RC STRAIN=K12;
RX PubMed=2844820; DOI=10.1016/s0021-9258(19)37644-6;
RA Metzger S., Dror I.B., Aizenman E., Schreiber G., Toone M., Friesen J.D.,
RA Cashel M., Glaser G.;
RT "The nucleotide sequence and characterization of the relA gene of
RT Escherichia coli.";
RL J. Biol. Chem. 263:15699-15704(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / MC1000 / ATCC 39531;
RX PubMed=8226627; DOI=10.1128/jb.175.21.6850-6856.1993;
RA Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E.;
RT "chpA and chpB, Escherichia coli chromosomal homologs of the pem locus
RT responsible for stable maintenance of plasmid R100.";
RL J. Bacteriol. 175:6850-6856(1993).
RN [3]
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 [4]
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 [5]
RP FUNCTION, CLEAVAGE BY THE CLPPA PROTEASE, INTERACTION WITH MAZF, INDUCTION,
RP AND OPERON STRUCTURE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=8650219; DOI=10.1073/pnas.93.12.6059;
RA Aizenman E., Engelberg-Kulka H., Glaser G.;
RT "An Escherichia coli chromosomal 'addiction module' regulated by guanosine
RT 3',5'-bispyrophosphate: a model for programmed bacterial cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6059-6063(1996).
RN [6]
RP TRANSCRIPTION REGULATION, DNA-BINDING, AND SUBUNIT.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=11071896; DOI=10.1074/jbc.m008832200;
RA Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G.;
RT "The regulation of the Escherichia coli mazEF promoter involves an unusual
RT alternating palindrome.";
RL J. Biol. Chem. 276:5975-5984(2001).
RN [7]
RP FUNCTION AS AN ANTITOXIN.
RC STRAIN=K12;
RX PubMed=12123459; DOI=10.1046/j.1365-2958.2002.03027.x;
RA Pedersen K., Christensen S.K., Gerdes K.;
RT "Rapid induction and reversal of a bacteriostatic condition by controlled
RT expression of toxins and antitoxins.";
RL Mol. Microbiol. 45:501-510(2002).
RN [8]
RP FUNCTION, SUBUNIT, AND DNA-BINDING.
RX PubMed=12533537; DOI=10.1074/jbc.m209855200;
RA Lah J., Marianovsky I., Glaser G., Engelberg-Kulka H., Kinne J., Wyns L.,
RA Loris R.;
RT "Recognition of the intrinsically flexible addiction antidote MazE by a
RT dromedary single domain antibody fragment. Structure, thermodynamics of
RT binding, stability, and influence on interactions with DNA.";
RL J. Biol. Chem. 278:14101-14111(2003).
RN [9]
RP INDUCTION, POSSIBLE CLEAVAGE BY THE LON PROTEASE, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=12972253; DOI=10.1016/s0022-2836(03)00922-7;
RA Christensen S.K., Pedersen K., Hansen F.G., Gerdes K.;
RT "Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK
RT cleave translated RNAs and are counteracted by tmRNA.";
RL J. Mol. Biol. 332:809-819(2003).
RN [10]
RP ROLE IN PROGRAMMED CELL DEATH.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=15576778; DOI=10.1128/jb.186.24.8295-8300.2004;
RA Amitai S., Yassin Y., Engelberg-Kulka H.;
RT "MazF-mediated cell death in Escherichia coli: a point of no return.";
RL J. Bacteriol. 186:8295-8300(2004).
RN [11]
RP FUNCTION IN PHAGE IMMUNITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / JM109 / ATCC 53323, K12 / K38 / S26, and
RC K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=15316771; DOI=10.1007/s00438-004-1048-y;
RA Hazan R., Engelberg-Kulka H.;
RT "Escherichia coli mazEF-mediated cell death as a defense mechanism that
RT inhibits the spread of phage P1.";
RL Mol. Genet. Genomics 272:227-234(2004).
RN [12]
RP INDUCTION, AND OPERON STRUCTURE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574, and
RC K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16390452; DOI=10.1111/j.1365-2958.2005.04956.x;
RA Gross M., Marianovsky I., Glaser G.;
RT "MazG -- a regulator of programmed cell death in Escherichia coli.";
RL Mol. Microbiol. 59:590-601(2006).
RN [13]
RP DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=20005847; DOI=10.1016/j.molcel.2009.11.024;
RA Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J.,
RA Walker G.C.;
RT "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia
RT coli.";
RL Mol. Cell 36:845-860(2009).
RN [14]
RP FUNCTION IN CELL DEATH, FUNCTION IN BIOFILM FORMATION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=19707553; DOI=10.1371/journal.pone.0006785;
RA Kolodkin-Gal I., Verdiger R., Shlosberg-Fedida A., Engelberg-Kulka H.;
RT "A differential effect of E. coli toxin-antitoxin systems on cell death in
RT liquid media and biofilm formation.";
RL PLoS ONE 4:E6785-E6785(2009).
RN [15]
RP FUNCTION.
RX PubMed=21419338; DOI=10.1016/j.molcel.2011.02.023;
RA Belitsky M., Avshalom H., Erental A., Yelin I., Kumar S., London N.,
RA Sperber M., Schueler-Furman O., Engelberg-Kulka H.;
RT "The Escherichia coli extracellular death factor EDF induces the
RT endoribonucleolytic activities of the toxins MazF and ChpBK.";
RL Mol. Cell 41:625-635(2011).
RN [16]
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 [17]
RP CLEAVAGE BY LON AND CLPP.
RC STRAIN=K12 / BW25113, and K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=24375411; DOI=10.1074/jbc.m113.510511;
RA Tripathi A., Dewan P.C., Siddique S.A., Varadarajan R.;
RT "MazF-induced growth inhibition and persister generation in Escherichia
RT coli.";
RL J. Biol. Chem. 289:4191-4205(2014).
RN [18]
RP REVIEW.
RX PubMed=19215780; DOI=10.1016/s0079-6603(08)00812-x;
RA Yamaguchi Y., Inouye M.;
RT "mRNA interferases, sequence-specific endoribonucleases from the toxin-
RT antitoxin systems.";
RL Prog. Mol. Biol. Transl. Sci. 85:467-500(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH AN ANTIBODY
RP FRAGMENT, DNA-BINDING, AND MUTAGENESIS OF ARG-8 AND ARG-16.
RX PubMed=12743116; DOI=10.1074/jbc.m302336200;
RA Loris R., Marianovsky I., Lah J., Laeremans T., Engelberg-Kulka H.,
RA Glaser G., Muyldermans S., Wyns L.;
RT "Crystal structure of the intrinsically flexible addiction antidote MazE.";
RL J. Biol. Chem. 278:28252-28257(2003).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), AND SUBUNIT.
RX PubMed=12718874; DOI=10.1016/s1097-2765(03)00097-2;
RA Kamada K., Hanaoka F., Burley S.K.;
RT "Crystal structure of the MazE/MazF complex: molecular bases of antidote-
RT toxin recognition.";
RL Mol. Cell 11:875-884(2003).
RN [21]
RP STRUCTURE BY NMR OF 2-50 IN COMPLEX WITH DNA, FUNCTION, SUBUNIT, AND
RP DNA-BINDING.
RX PubMed=25564525; DOI=10.1093/nar/gku1352;
RA Zorzini V., Buts L., Schrank E., Sterckx Y.G., Respondek M.,
RA Engelberg-Kulka H., Loris R., Zangger K., van Nuland N.A.;
RT "Escherichia coli antitoxin MazE as transcription factor: insights into
RT MazE-DNA binding.";
RL Nucleic Acids Res. 43:1241-1256(2015).
CC -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system.
CC Labile antitoxin that binds to the MazF endoribonuclease toxin and
CC neutralizes its endoribonuclease activity. Is considered to be an
CC 'addiction' molecule as the cell dies in its absence. Toxicity results
CC when the levels of MazE decrease in the cell, leading to mRNA
CC degradation. This effect can be rescued by expression of MazE, but
CC after 6 hours in rich medium the overexpression of MazF leads to
CC programmed cell death. Cell growth and viability are not affected when
CC MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the
CC promoter region of the mazE-mazF operon to inhibit their own
CC transcription (PubMed:8650219). There are 3 operators to which MazE
CC binds (PubMed:12533537). MazE has higher affinity for promoter DNA in
CC the presence of MazF (PubMed:25564525). {ECO:0000269|PubMed:11071896,
CC ECO:0000269|PubMed:12123459, ECO:0000269|PubMed:12533537,
CC ECO:0000269|PubMed:19707553, ECO:0000269|PubMed:21419338,
CC ECO:0000269|PubMed:25564525, ECO:0000269|PubMed:8650219}.
CC -!- FUNCTION: Cell death governed by the MazE-MazF and DinJ-YafQ TA systems
CC seems to play a role in biofilm formation, while MazE-MazF is also
CC implicated in cell death in liquid media. {ECO:0000269|PubMed:15576778,
CC ECO:0000269|PubMed:19707553}.
CC -!- FUNCTION: Might also serve to protect cells against bacteriophage; in
CC the presence of MazE-MazF fewer P1 phage are produced than in a
CC disrupted strain. For strain K38 most wild-type cells are killed but
CC not by phage lysis; it was suggested that MazE-MazF causes P1 phage
CC exclusion from the bacterial population. This phenomenon is strain
CC dependent. {ECO:0000269|PubMed:15316771}.
CC -!- SUBUNIT: Probably forms a homodimer in the absence of MazF; binds DNA
CC as a homodimer (PubMed:25564525, PubMed:12533537). Forms a
CC heterohexamer composed of alternating toxin and antitoxin homodimers
CC MazF(2)-MazE(2)-MazF(2). {ECO:0000269|PubMed:11071896,
CC ECO:0000269|PubMed:12533537, ECO:0000269|PubMed:12718874,
CC ECO:0000269|PubMed:12743116, ECO:0000269|PubMed:25564525,
CC ECO:0000269|PubMed:8650219}.
CC -!- INDUCTION: Expressed in exponentially growing cells. Induction has been
CC reported to occur after amino acid starvation in a ppGpp-independent
CC fashion and to be Lon protease-dependent (PubMed:12972253), but also to
CC not occur after amino acid starvation and to be regulated by ppGpp
CC (PubMed:8650219). MazE alone and in combination with MazF, represses
CC transcription of the mazE-mazF operon. Fis activates transcription.
CC Part of the relA-mazE-mazF-mazG operon, there is also a second mazE-
CC mazF specific promoter which is negatively autoregulated. This operon
CC induced by ectopic expression of toxin RelE; induction of this operon
CC by amino acid starvation requires the relBEF operon (PubMed:23432955).
CC {ECO:0000269|PubMed:11071896, ECO:0000269|PubMed:12972253,
CC ECO:0000269|PubMed:16390452, ECO:0000269|PubMed:23432955,
CC ECO:0000269|PubMed:8650219}.
CC -!- PTM: Degraded by the ClpPA and Lon proteases.
CC {ECO:0000269|PubMed:12972253, ECO:0000269|PubMed:24375411,
CC ECO:0000269|PubMed:8650219}.
CC -!- DISRUPTION PHENOTYPE: Decreased sensitivity to dramatic intracellular
CC increases of ppGpp. Double mazE-mazF disruptions survive high
CC temperature, various DNA-damaging agents and H(2)O(2) exposure better
CC than wild-type cells. They produce more P1 phage than wild-type cells,
CC while introduction of lysogens into a growing non-lysogenic disruption
CC culture is lethal (PubMed:15316771). Double mazE-mazF disruptions show
CC reduced biofilm formation, and survive antibiotic treatment in log
CC phase better than wild-type cells. Cells missing mazE-mazF survive
CC hydroxyurea treatment better than wild-type; further disruption of
CC relE-relB and tonB yields even better survival (PubMed:20005847).
CC {ECO:0000269|PubMed:12972253, ECO:0000269|PubMed:15316771,
CC ECO:0000269|PubMed:19707553, ECO:0000269|PubMed:20005847}.
CC -!- SIMILARITY: Belongs to the PemI family. {ECO:0000305}.
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DR EMBL; D16450; BAA41177.1; -; Genomic_DNA.
DR EMBL; J04039; AAA03238.1; -; Unassigned_DNA.
DR EMBL; U29580; AAA69293.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75825.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76857.1; -; Genomic_DNA.
DR PIR; B31996; BVECZE.
DR RefSeq; NP_417263.1; NC_000913.3.
DR RefSeq; WP_000581937.1; NZ_STEB01000030.1.
DR PDB; 1MVF; X-ray; 1.65 A; D/E=1-82.
DR PDB; 1UB4; X-ray; 1.70 A; C=1-82.
DR PDB; 2MRN; NMR; -; A/B=2-50.
DR PDB; 2MRU; NMR; -; A/B=2-50.
DR PDB; 5CQX; X-ray; 1.63 A; C=68-82.
DR PDB; 5CQY; X-ray; 2.48 A; C=68-82.
DR PDBsum; 1MVF; -.
DR PDBsum; 1UB4; -.
DR PDBsum; 2MRN; -.
DR PDBsum; 2MRU; -.
DR PDBsum; 5CQX; -.
DR PDBsum; 5CQY; -.
DR AlphaFoldDB; P0AE72; -.
DR BMRB; P0AE72; -.
DR SMR; P0AE72; -.
DR ComplexPortal; CPX-1086; MazEF toxin-antitoxin complex.
DR IntAct; P0AE72; 10.
DR STRING; 511145.b2783; -.
DR PaxDb; P0AE72; -.
DR PRIDE; P0AE72; -.
DR ABCD; P0AE72; 1 sequenced antibody.
DR EnsemblBacteria; AAC75825; AAC75825; b2783.
DR EnsemblBacteria; BAE76857; BAE76857; BAE76857.
DR GeneID; 66673350; -.
DR GeneID; 947245; -.
DR KEGG; ecj:JW2754; -.
DR KEGG; eco:b2783; -.
DR PATRIC; fig|1411691.4.peg.3952; -.
DR EchoBASE; EB0566; -.
DR eggNOG; COG2336; Bacteria.
DR HOGENOM; CLU_150554_1_0_6; -.
DR InParanoid; P0AE72; -.
DR OMA; WGNSPSV; -.
DR PhylomeDB; P0AE72; -.
DR BioCyc; EcoCyc:EG10571-MON; -.
DR BioCyc; MetaCyc:EG10571-MON; -.
DR EvolutionaryTrace; P0AE72; -.
DR PRO; PR:P0AE72; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0003690; F:double-stranded DNA binding; IMP:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:CAFA.
DR GO; GO:0097351; F:toxin sequestering activity; IDA:CAFA.
DR GO; GO:0040008; P:regulation of growth; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:ComplexPortal.
DR GO; GO:0044010; P:single-species biofilm formation; IDA:ComplexPortal.
DR DisProt; DP01291; -.
DR InterPro; IPR007159; SpoVT-AbrB_dom.
DR InterPro; IPR037914; SpoVT-AbrB_sf.
DR Pfam; PF04014; MazE_antitoxin; 1.
DR SMART; SM00966; SpoVT_AbrB; 1.
DR SUPFAM; SSF89447; SSF89447; 1.
DR PROSITE; PS51740; SPOVT_ABRB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor;
KW Toxin-antitoxin system; Transcription; Transcription regulation.
FT CHAIN 1..82
FT /note="Antitoxin MazE"
FT /id="PRO_0000089649"
FT DOMAIN 4..49
FT /note="SpoVT-AbrB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01076"
FT MUTAGEN 8
FT /note="R->A: Binds poorly to DNA."
FT /evidence="ECO:0000269|PubMed:12743116"
FT MUTAGEN 16
FT /note="R->A: Does not bind to DNA."
FT /evidence="ECO:0000269|PubMed:12743116"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:1UB4"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:1UB4"
FT HELIX 19..24
FT /evidence="ECO:0007829|PDB:1UB4"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2MRN"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:2MRN"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:1UB4"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:1UB4"
SQ SEQUENCE 82 AA; 9356 MW; CD452A9AA4FB362E CRC64;
MIHSSVKRWG NSPAVRIPAT LMQALNLNID DEVKIDLVDG KLIIEPVRKE PVFTLAELVN
DITPENLHEN IDWGEPKDKE VW
