CCDB_ECOLI
ID CCDB_ECOLI Reviewed; 101 AA.
AC P62554; P05703;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Toxin CcdB;
DE AltName: Full=Cytotoxic protein CcdB;
DE AltName: Full=LynB;
DE AltName: Full=Protein G;
DE AltName: Full=Protein LetD;
GN Name=ccdB; Synonyms=G, letB, letD; OrderedLocusNames=ECOK12F043;
OS Escherichia coli (strain K12).
OG Plasmid F.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ROLE IN CELL DEATH.
RX PubMed=6327993; DOI=10.1016/0022-2836(84)90086-x;
RA Miki T., Yoshioka K., Horiuchi T.;
RT "Control of cell division by sex factor F in Escherichia coli. I. The
RT 42.84-43.6 F segment couples cell division of the host bacteria with
RT replication of plasmid DNA.";
RL J. Mol. Biol. 174:605-625(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Eichenlaub R.;
RT "F plasmid DNA complete mini-F region (F coordinates 40.301F to 49.869F).";
RL Submitted (AUG-1986) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / CR63;
RA Shimizu H., Saitoh Y., Suda Y., Uehara K., Sampei G., Mizobuchi K.;
RT "Complete nucleotide sequence of the F plasmid: its implications for
RT organization and diversification of plasmid genomes.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 1-15, FUNCTION IN TRANSCRIPTIONAL REGULATION,
RP DNA-BINDING, AND SUBUNIT.
RX PubMed=2651399; DOI=10.1128/jb.171.5.2353-2360.1989;
RA Tam J.E., Kline B.C.;
RT "Control of the ccd operon in plasmid F.";
RL J. Bacteriol. 171:2353-2360(1989).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=6227479; DOI=10.1002/j.1460-2075.1983.tb01672.x;
RA Karoui H., Bex F., Dreze P., Couturier M.;
RT "Ham22, a mini-F mutation which is lethal to host cell and promotes recA-
RT dependent induction of lambdoid prophage.";
RL EMBO J. 2:1863-1868(1983).
RN [6]
RP ROLE IN PLASMID MAINTENANCE, AND DISRUPTION PHENOTYPE.
RX PubMed=6308648; DOI=10.1073/pnas.80.15.4784;
RA Ogura T., Hiraga S.;
RT "Mini-F plasmid genes that couple host cell division to plasmid
RT proliferation.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:4784-4788(1983).
RN [7]
RP FUNCTION IN TRANSCRIPTIONAL REGULATION, DNA-BINDING, AND SUBUNIT.
RX PubMed=2615761; DOI=10.1007/bf00261153;
RA Tam J.E., Kline B.C.;
RT "The F plasmid ccd autorepressor is a complex of CcdA and CcdB proteins.";
RL Mol. Gen. Genet. 219:26-32(1989).
RN [8]
RP FUNCTION AS A TOXIN, FUNCTION IN DNA BREAKAGE, AND INHIBITION BY CCDA.
RX PubMed=1324324; DOI=10.1016/0022-2836(92)90629-x;
RA Bernard P., Couturier M.;
RT "Cell killing by the F plasmid CcdB protein involves poisoning of DNA-
RT topoisomerase II complexes.";
RL J. Mol. Biol. 226:735-745(1992).
RN [9]
RP CHARACTERIZATION OF REJUVENATION ACTIVITY, AND ATP REQUIRED FOR DNA
RP BREAKAGE.
RX PubMed=8254658; DOI=10.1006/jmbi.1993.1609;
RA Bernard P., Kezdy K.E., Van Melderen L., Steyaert J., Wyns L., Pato M.L.,
RA Higgins P.N., Couturier M.;
RT "The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by
RT gyrase.";
RL J. Mol. Biol. 234:534-541(1993).
RN [10]
RP HALF-LIFE.
RX PubMed=8022284; DOI=10.1111/j.1365-2958.1994.tb00391.x;
RA Van Melderen L., Bernard P., Couturier M.;
RT "Lon-dependent proteolysis of CcdA is the key control for activation of
RT CcdB in plasmid-free segregant bacteria.";
RL Mol. Microbiol. 11:1151-1157(1994).
RN [11]
RP MUTAGENESIS OF GLN-21; TRP-61; TRP-99; GLY-100 AND ILE-101.
RX PubMed=7623659; DOI=10.1111/j.1365-2958.1995.tb02278.x;
RA Bahassi E.M., Salmon M.A., Van Melderen L., Bernard P., Couturier M.;
RT "F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic
RT proteins which retain their regulatory functions.";
RL Mol. Microbiol. 15:1031-1037(1995).
RN [12]
RP FUNCTION AS A TOXIN, FUNCTION IN DNA BREAKAGE, REJUVENATION, AND SUBUNIT.
RX PubMed=8604132; DOI=10.1006/jmbi.1996.0102;
RA Maki S., Takiguchi S., Horiuchi T., Sekimizu K., Miki T.;
RT "Partner switching mechanisms in inactivation and rejuvenation of
RT Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA
RT (CcdA).";
RL J. Mol. Biol. 256:473-482(1996).
RN [13]
RP MODE OF TRANSCRIPTIONAL REGULATION.
RX PubMed=11454201; DOI=10.1046/j.1365-2958.2001.02492.x;
RA Afif H., Allali N., Couturier M., Van Melderen L.;
RT "The ratio between CcdA and CcdB modulates the transcriptional repression
RT of the ccd poison-antidote system.";
RL Mol. Microbiol. 41:73-82(2001).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS), AND SUBUNIT.
RX PubMed=9917404; DOI=10.1006/jmbi.1998.2395;
RA Loris R., Dao-Thi M.-H., Bahassi E.M., van Melderen L., Poortmans F.,
RA Liddington R., Couturier M., Wyns L.;
RT "Crystal structure of CcdB, a topoisomerase poison from E. coli.";
RL J. Mol. Biol. 285:1667-1677(1999).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH GYRA.
RX PubMed=15854646; DOI=10.1016/j.jmb.2005.03.049;
RA Dao-Thi M.H., Van Melderen L., De Genst E., Afif H., Buts L., Wyns L.,
RA Loris R.;
RT "Molecular basis of gyrase poisoning by the addiction toxin CcdB.";
RL J. Mol. Biol. 348:1091-1102(2005).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), AND SUBUNIT.
RX PubMed=19647513; DOI=10.1016/j.molcel.2009.05.025;
RA De Jonge N., Garcia-Pino A., Buts L., Haesaerts S., Charlier D.,
RA Zangger K., Wyns L., De Greve H., Loris R.;
RT "Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered
RT protein domain.";
RL Mol. Cell 35:154-163(2009).
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system,
CC functioning in plasmid maintainence. Responsible for the post-
CC segregational killing (PSK) of plasmid-free cells, also referred to as
CC a plasmid addiction system. Half-life of over 2 hours. Cell killing by
CC CcdB is accompanied by filamentation, defects in chromosome and plasmid
CC segregation, defects in cell division, formation of anucleate cells,
CC decreased DNA synthesis and plasmid loss. Interferes with the activity
CC of DNA gyrase, inducing it to form a covalent GyrA-DNA complex that
CC cannot be resolved, thus promoting breakage of plasmid and chromosomal
CC DNA. DNA breakage requires hydrolyzable ATP. Toxicity is inhibited by
CC labile antitoxin CcdA, which blocks the activity of CcdB; CcdA also
CC removes bound CcdB protein from the CcdB-GyrA complex by forming a
CC CcdA-CcdB complex, a process termed rejuvenation. Also acts to inhibit
CC partitioning of the chromosomal DNA. Functions as a transcriptional
CC corepressor for the ccdAB operon, repression also requires CcdA.
CC {ECO:0000269|PubMed:1324324, ECO:0000269|PubMed:2615761,
CC ECO:0000269|PubMed:2651399, ECO:0000269|PubMed:6308648,
CC ECO:0000269|PubMed:6327993, ECO:0000269|PubMed:8604132}.
CC -!- SUBUNIT: Homodimer. Forms a complex with GyrA, probably a tetramer
CC GyrA(2)CcdB(2), in which GyrA is inactive. Forms a complex with
CC antitoxin CcdA; there are both high- and low-affinity binding sites for
CC CcdA such that both CcdA-CcdB(2) and CcdA(2)CcdB(2) complexes can form.
CC The CcdA-CcdB(2) trimer is sufficient for rejuvenation, whereas maximal
CC operon repression occurs with CcdA(2)CcdB(2). When the CcdA:CcdB ratio
CC is lower than 1, a CcdA(2)-CcdB(4) complex is formed which is devoid of
CC repression activity. In this case repression is alleviated and both
CC proteins are produced. {ECO:0000269|PubMed:15854646,
CC ECO:0000269|PubMed:19647513, ECO:0000269|PubMed:2615761,
CC ECO:0000269|PubMed:2651399, ECO:0000269|PubMed:8604132,
CC ECO:0000269|PubMed:9917404}.
CC -!- INTERACTION:
CC P62554; P62552: ccdA; NbExp=6; IntAct=EBI-25647730, EBI-25647704;
CC P62554; P0AES4: gyrA; NbExp=3; IntAct=EBI-25647730, EBI-547129;
CC -!- DISRUPTION PHENOTYPE: Disruption of both ccdA and ccdB has no
CC phenotype, except for increased plasmid loss.
CC {ECO:0000269|PubMed:6227479, ECO:0000269|PubMed:6308648}.
CC -!- SIMILARITY: Belongs to the CcdB toxin family. {ECO:0000305}.
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DR EMBL; X00594; CAA25244.1; -; Genomic_DNA.
DR EMBL; M12987; AAA24899.1; -; Genomic_DNA.
DR EMBL; AP001918; BAA97913.1; -; Genomic_DNA.
DR PIR; T00238; T00238.
DR RefSeq; NP_061422.1; NC_002483.1.
DR RefSeq; WP_001159868.1; NZ_STEB01000056.1.
DR RefSeq; YP_003108267.1; NC_013122.1.
DR PDB; 1VUB; X-ray; 2.60 A; A/B/C/D=1-101.
DR PDB; 1X75; X-ray; 2.80 A; C/D=1-101.
DR PDB; 2VUB; X-ray; 2.45 A; A/B/C/D/E/F/G/H=1-101.
DR PDB; 3G7Z; X-ray; 2.35 A; A/B=1-101.
DR PDB; 3HPW; X-ray; 1.45 A; A/B=1-101.
DR PDB; 3VUB; X-ray; 1.40 A; A=1-101.
DR PDB; 4VUB; X-ray; 1.45 A; A=1-101.
DR PDBsum; 1VUB; -.
DR PDBsum; 1X75; -.
DR PDBsum; 2VUB; -.
DR PDBsum; 3G7Z; -.
DR PDBsum; 3HPW; -.
DR PDBsum; 3VUB; -.
DR PDBsum; 4VUB; -.
DR AlphaFoldDB; P62554; -.
DR SASBDB; P62554; -.
DR SMR; P62554; -.
DR ComplexPortal; CPX-5906; CcdB-poisoned gyrase complex.
DR ComplexPortal; CPX-5908; CcdAB toxin-antitoxin complex.
DR IntAct; P62554; 2.
DR PRIDE; P62554; -.
DR EvolutionaryTrace; P62554; -.
DR PRO; PR:P62554; -.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0017053; C:transcription repressor complex; IDA:ComplexPortal.
DR GO; GO:0008657; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) inhibitor activity; IEA:InterPro.
DR GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; IDA:ComplexPortal.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:ComplexPortal.
DR GO; GO:0006276; P:plasmid maintenance; IEA:InterPro.
DR Gene3D; 2.30.30.110; -; 1.
DR InterPro; IPR002712; CcdB.
DR InterPro; IPR011067; Plasmid_toxin/cell-grow_inhib.
DR Pfam; PF01845; CcdB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Plasmid; Repressor;
KW Toxin-antitoxin system; Transcription; Transcription regulation.
FT CHAIN 1..101
FT /note="Toxin CcdB"
FT /id="PRO_0000068386"
FT MUTAGEN 21
FT /note="Q->L,S,Y: No phenotype."
FT /evidence="ECO:0000269|PubMed:7623659"
FT MUTAGEN 61
FT /note="W->L,Q,S,Y: No phenotype."
FT /evidence="ECO:0000269|PubMed:7623659"
FT MUTAGEN 99..101
FT /note="Missing: Loss of toxicity, no decrease in protein
FT stability. Still represses ccdAB operon, still forms
FT complex with CcdA."
FT MUTAGEN 99
FT /note="W->L,Q,S,Y: Loss of toxicity."
FT /evidence="ECO:0000269|PubMed:7623659"
FT MUTAGEN 100
FT /note="G->E,R: Loss of toxicity, no decrease in protein
FT stability. Still represses ccdAB operon, still forms
FT complex with CcdA."
FT /evidence="ECO:0000269|PubMed:7623659"
FT MUTAGEN 101
FT /note="I->R: Loss of toxicity."
FT /evidence="ECO:0000269|PubMed:7623659"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 30..42
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:3VUB"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:3VUB"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3VUB"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:3VUB"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:3VUB"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:3VUB"
FT HELIX 87..99
FT /evidence="ECO:0007829|PDB:3VUB"
SQ SEQUENCE 101 AA; 11707 MW; 566AF6681DFE94FE CRC64;
MQFKVYTYKR ESRYRLFVDV QSDIIDTPGR RMVIPLASAR LLSDKVSREL YPVVHIGDES
WRMMTTDMAS VPVSVIGEEV ADLSHRENDI KNAINLMFWG I
