CCDA_ECOLI
ID CCDA_ECOLI Reviewed; 72 AA.
AC P62552; P05702;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Antitoxin CcdA;
DE AltName: Full=LynA;
DE AltName: Full=Protein H;
DE AltName: Full=Protein LetA;
GN Name=ccdA; Synonyms=H, letA; OrderedLocusNames=ECOK12F042;
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 AN ANTITOXIN.
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.
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 CLEAVAGE BY LON PROTEASE.
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 FUNCTION IN 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 [12]
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 [13]
RP STRUCTURE BY NMR FREE AND BOUND TO DNA, SUBUNIT, DNA-BINDING, AND
RP MUTAGENESIS OF VAL-22; ARG-70 AND 62-ASN--TRP-72.
RX PubMed=17007877; DOI=10.1016/j.jmb.2006.08.082;
RA Madl T., Van Melderen L., Mine N., Respondek M., Oberer M., Keller W.,
RA Khatai L., Zangger K.;
RT "Structural basis for nucleic acid and toxin recognition of the bacterial
RT antitoxin CcdA.";
RL J. Mol. Biol. 364:170-185(2006).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 37-72, FUNCTION AS AN ANTITOXIN,
RP SUBUNIT, AND DNA-BINDING.
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: Antitoxin component of a type II toxin-antitoxin (TA) system
CC which inhibits the post-segregational killing (PSK) of plasmid-free
CC cells, also referred to as a plasmid addiction system. Labile antitoxin
CC with a half-life of about 1 hour in the presence of CcdB. Binds to and
CC blocks the activity of CcdB; will also remove bound CcdB protein from
CC the CcdB-GyrA complex by forming a CcdA-CcdB complex, a process termed
CC rejuvenation. The N-terminal 36 residues are not required for
CC rejuventation. Functions as a transcriptional corepressor for the ccdAB
CC operon, repression also requires CcdB. {ECO:0000269|PubMed:1324324,
CC ECO:0000269|PubMed:19647513, 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 in solution and when bound to DNA. Three CcdA
CC homodimers bind to the promoter region and contact each other via Val-
CC 22. Forms a complex with toxin CcdB; there are both high- and low-
CC affinity binding sites for CcdA such that both CcdA-CcdB(2) and
CC CcdA(2)CcdB(2) complexes can form. The CcdA-CcdB(2) trimer is
CC sufficient for rejuvenation, whereas maximal operon repression occurs
CC with CcdA(2)CcdB(2). When the CcdA:CcdB ratio is lower than 1, a
CC CcdA(2)-CcdB(4) complex is formed which is devoid of repression
CC activity. In this case repression is alleviated and both proteins are
CC produced. {ECO:0000269|PubMed:17007877, ECO:0000269|PubMed:19647513,
CC ECO:0000269|PubMed:2615761, ECO:0000269|PubMed:2651399,
CC ECO:0000269|PubMed:8604132}.
CC -!- INTERACTION:
CC P62552; P62554: ccdB; NbExp=6; IntAct=EBI-25647704, EBI-25647730;
CC -!- PTM: Degraded by the Lon protease.
CC -!- DISRUPTION PHENOTYPE: Leads to cell death and induction of the SOS
CC pathway. Additional disruption of ccdB reverses this effect, i.e. no
CC cell death nor induction of the SOS response. The double disruption
CC leads to increased plasmid loss. {ECO:0000269|PubMed:6227479,
CC ECO:0000269|PubMed:6308648}.
CC -!- SIMILARITY: Belongs to the CcdA antitoxin family. {ECO:0000305}.
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DR EMBL; X00594; CAA25243.1; -; Genomic_DNA.
DR EMBL; M12987; AAA24898.1; -; Genomic_DNA.
DR EMBL; AP001918; BAA97912.1; -; Genomic_DNA.
DR PIR; T00237; T00237.
DR RefSeq; NP_061421.1; NC_002483.1.
DR RefSeq; WP_000813634.1; NZ_SSUU01000069.1.
DR RefSeq; YP_001816480.1; NC_010558.1.
DR RefSeq; YP_003108266.1; NC_013122.1.
DR RefSeq; YP_003162544.1; NC_013175.1.
DR RefSeq; YP_003829105.1; NC_014384.1.
DR RefSeq; YP_003829230.1; NC_014385.1.
DR RefSeq; YP_006940499.1; NC_019000.1.
DR RefSeq; YP_424850.1; NC_007635.1.
DR RefSeq; YP_788019.1; NC_008460.1.
DR PDB; 2ADL; NMR; -; A/B=1-72.
DR PDB; 2ADN; NMR; -; A/B=1-72.
DR PDB; 2H3A; NMR; -; A/B=1-72.
DR PDB; 2H3C; NMR; -; A/B=1-72.
DR PDB; 3G7Z; X-ray; 2.35 A; C/D=37-72.
DR PDB; 3HPW; X-ray; 1.45 A; C=37-72.
DR PDBsum; 2ADL; -.
DR PDBsum; 2ADN; -.
DR PDBsum; 2H3A; -.
DR PDBsum; 2H3C; -.
DR PDBsum; 3G7Z; -.
DR PDBsum; 3HPW; -.
DR AlphaFoldDB; P62552; -.
DR SASBDB; P62552; -.
DR SMR; P62552; -.
DR ComplexPortal; CPX-5908; CcdAB toxin-antitoxin complex.
DR IntAct; P62552; 2.
DR PRIDE; P62552; -.
DR EvolutionaryTrace; P62552; -.
DR PRO; PR:P62552; -.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0017053; C:transcription repressor complex; IDA:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:ComplexPortal.
DR DisProt; DP00928; -.
DR InterPro; IPR009956; Post-segregation_anti-tox_CcdA.
DR Pfam; PF07362; CcdA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; DNA-binding; Plasmid; Repressor;
KW Toxin-antitoxin system; Transcription; Transcription regulation.
FT CHAIN 1..72
FT /note="Antitoxin CcdA"
FT /id="PRO_0000068383"
FT REGION 1..36
FT /note="Not required for antitoxin activity, or
FT rejuvenation"
FT REGION 3..40
FT /note="Interaction with DNA"
FT REGION 41..72
FT /note="Interaction with CcdB"
FT MUTAGEN 22
FT /note="V->H: Partial loss of operon autoregulation."
FT /evidence="ECO:0000269|PubMed:17007877"
FT MUTAGEN 62..72
FT /note="Missing: Loss of protein stability."
FT /evidence="ECO:0000269|PubMed:17007877"
FT MUTAGEN 70
FT /note="R->K: Increased protein stability."
FT /evidence="ECO:0000269|PubMed:17007877"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:2ADL"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:2ADL"
FT HELIX 14..19
FT /evidence="ECO:0007829|PDB:2ADL"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:2ADL"
FT HELIX 41..62
FT /evidence="ECO:0007829|PDB:3HPW"
FT HELIX 65..69
FT /evidence="ECO:0007829|PDB:3HPW"
SQ SEQUENCE 72 AA; 8372 MW; BFA1C8AEFEDF511B CRC64;
MKQRITVTVD SDSYQLLKAY DVNISGLVST TMQNEARRLR AERWKAENQE GMAEVARFIE
MNGSFADENR DW
