CDIA4_ECO5C
ID CDIA4_ECO5C Reviewed; 377 AA.
AC B3BM80;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Deoxyribonuclease CdiA-o11;
DE Short=DNase CdiA;
DE EC=3.1.-.- {ECO:0000269|PubMed:23236156};
DE AltName: Full=CdiA-o11-EC869;
DE AltName: Full=Toxin CdiA;
GN Name=cdiA4; Synonyms=cdiA-CTo11; ORFNames=ECH7EC869_5883;
OS Escherichia coli O157:H7 (strain EC869).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=478008;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=EC869;
RX PubMed=21421787; DOI=10.1128/aem.02554-10;
RA Eppinger M., Mammel M.K., Leclerc J.E., Ravel J., Cebula T.A.;
RT "Genome signatures of Escherichia coli O157:H7 isolates from the bovine
RT host reservoir.";
RL Appl. Environ. Microbiol. 77:2916-2925(2011).
RN [2]
RP FUNCTION, INTERACTION WITH CDII, AND SUBUNIT.
RC STRAIN=EC869;
RX PubMed=21829394; DOI=10.1371/journal.pgen.1002217;
RA Poole S.J., Diner E.J., Aoki S.K., Braaten B.A., t'Kint de Roodenbeke C.,
RA Low D.A., Hayes C.S.;
RT "Identification of functional toxin/immunity genes linked to contact-
RT dependent growth inhibition (CDI) and rearrangement hotspot (Rhs)
RT systems.";
RL PLoS Genet. 7:E1002217-E1002217(2011).
RN [3]
RP FUNCTION, REQUIRES PMF FOR TRANSLOCATION, AND SUBCELLULAR LOCATION.
RC STRAIN=EC869;
RX PubMed=25174572; DOI=10.1111/mmi.12779;
RA Ruhe Z.C., Nguyen J.Y., Beck C.M., Low D.A., Hayes C.S.;
RT "The proton-motive force is required for translocation of CDI toxins across
RT the inner membrane of target bacteria.";
RL Mol. Microbiol. 94:466-481(2014).
RN [4]
RP FUNCTION, IDENTIFICATION OF RECEPTOR FOR ENTRY INTO TARGET CELL CYTOPLASM,
RP AND DOMAIN.
RC STRAIN=EC869;
RX PubMed=26305955; DOI=10.1073/pnas.1512124112;
RA Willett J.L., Gucinski G.C., Fatherree J.P., Low D.A., Hayes C.S.;
RT "Contact-dependent growth inhibition toxins exploit multiple independent
RT cell-entry pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11341-11346(2015).
RN [5] {ECO:0007744|PDB:4G6U}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 88-377 IN COMPLEX WITH CDII AND
RP ZINC, FUNCTION, COFACTOR, SUBUNIT, DOMAIN, AND MUTAGENESIS OF GLU-257 AND
RP ASP-278.
RC STRAIN=EC869;
RX PubMed=23236156; DOI=10.1073/pnas.1216238110;
RA Morse R.P., Nikolakakis K.C., Willett J.L., Gerrick E., Low D.A.,
RA Hayes C.S., Goulding C.W.;
RT "Structural basis of toxicity and immunity in contact-dependent growth
RT inhibition (CDI) systems.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:21480-21485(2012).
RN [6] {ECO:0007744|PDB:4ZQW}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 322-332, DOMAIN, AND MUTAGENESIS
RP OF 322-LYS--THR-332; 322-LYS--GLU-330 AND 323-GLU--ARG-329.
RX PubMed=26449640; DOI=10.1016/j.jmb.2015.09.020;
RA Morse R.P., Willett J.L., Johnson P.M., Zheng J., Credali A., Iniguez A.,
RA Nowick J.S., Hayes C.S., Goulding C.W.;
RT "Diversification of beta-augmentation interactions between CDI
RT toxin/immunity proteins.";
RL J. Mol. Biol. 427:3766-3784(2015).
CC -!- FUNCTION: Toxic component of a toxin-immunity protein module, which
CC functions as a cellular contact-dependent growth inhibition (CDI)
CC system. CDI modules allow bacteria to communicate with and inhibit the
CC growth of closely related neighboring bacteria in a contact-dependent
CC fashion (PubMed:21829394, PubMed:25174572). The C-terminal 289 residues
CC (the CT fragment) has a strong DNase activity in the presence of
CC Zn(2+), completely degrading supercoiled and linear plasmids, and
CC inhibits growth. In the presence of Mg(2+) it nicks dsDNA
CC (PubMed:23236156). Toxic activity is neutralized by coexpression of the
CC cognate immunity protein CdiI-o11-EC869, but not by non-cognate
CC immunity proteins from other toxin-immunity modules or other strains of
CC E.coli (PubMed:21829394). Gains access to the cytoplasm of target cells
CC by using integral inner membrane protein YciB (PubMed:26305955).
CC {ECO:0000269|PubMed:21829394, ECO:0000269|PubMed:23236156,
CC ECO:0000269|PubMed:25174572, ECO:0000269|PubMed:26305955}.
CC -!- FUNCTION: Expression of this locus confers protection against other
CC bacteria carrying the locus. {ECO:0000269|PubMed:21829394}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:23236156};
CC Note=Bind 1 Zn(2+) per subunit. {ECO:0000269|PubMed:23236156};
CC -!- SUBUNIT: Interacts with cognate immunity protein CdiI-o11-EC869, which
CC blocks its toxic DNase activity. {ECO:0000269|PubMed:21829394,
CC ECO:0000269|PubMed:23236156}.
CC -!- SUBCELLULAR LOCATION: Target cell, target cell cytoplasm
CC {ECO:0000305|PubMed:25174572}. Note=Toxin translocation into the target
CC cell depends on the proton motive force of the target cell, but not on
CC tolA or tonB. {ECO:0000269|PubMed:25174572}.
CC -!- DOMAIN: A beta-hairpin (residues 322-332) fits into a pocket in cognate
CC immunity protein CdiI-o11 and helps confer immunity protein specificity
CC (PubMed:23236156, PubMed:26449640). The inner membrane translocation
CC domain (IMTD) targets the toxin to a specific target cell inner
CC membrane protein (YciB in this case), which delivers the toxin to the
CC target cell cytoplasm. Exchanging this IMTD between CdiA proteins
CC alters the inner membrane protein delivery system but not the CdiI
CC immunity protein, strongly suggesting CdiI recognizes only the toxic
CC domain (PubMed:26305955). {ECO:0000269|PubMed:23236156,
CC ECO:0000269|PubMed:26305955, ECO:0000269|PubMed:26449640}.
CC -!- CAUTION: The sequences characterized in (PubMed:21829394) and
CC crystallized in (PubMed:23236156) are actually derived from cdiA-
CC CTo11/cdiIo11, an orphan cdiA-CT/cdiI module that only encodes the cdiA
CC CT fragment and its associated cdiI. It is however identical to that
CC shown in this entry, which does have the elements necessary for gene
CC expression. {ECO:0000305|PubMed:21829394, ECO:0000305|PubMed:23236156}.
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DR EMBL; ABHU01000020; EDU89618.1; -; Genomic_DNA.
DR PDB; 4G6U; X-ray; 2.35 A; A=88-377.
DR PDB; 4ZQW; X-ray; 2.00 A; A/C=322-332.
DR PDBsum; 4G6U; -.
DR PDBsum; 4ZQW; -.
DR AlphaFoldDB; B3BM80; -.
DR SMR; B3BM80; -.
DR EnsemblBacteria; EDU89618; EDU89618; ECH7EC869_5883.
DR Proteomes; UP000004641; Unassembled WGS sequence.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd13444; CDI_toxin_EC869_like; 1.
DR InterPro; IPR033799; CDI_EC869-like.
DR InterPro; IPR006914; VENN_dom.
DR Pfam; PF04829; PT-VENN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Nuclease; Target cell cytoplasm;
KW Toxin; Virulence; Zinc.
FT CHAIN 1..377
FT /note="Deoxyribonuclease CdiA-o11"
FT /id="PRO_0000429689"
FT REGION 85..233
FT /note="Inner membrane translocation domain (IMTD), targets
FT to YciB"
FT /evidence="ECO:0000269|PubMed:26305955"
FT REGION 88..377
FT /note="CT domain, sufficient to interact with CdiI"
FT /evidence="ECO:0000305|PubMed:23236156"
FT REGION 222..377
FT /note="Has DNase activity in vivo, cannot be expressed in
FT the absence of CdiI"
FT /evidence="ECO:0000305|PubMed:23236156"
FT MOTIF 81..84
FT /note="VENN CT cleavage motif"
FT /evidence="ECO:0000305"
FT ACT_SITE 257
FT /evidence="ECO:0000305|PubMed:23236156"
FT ACT_SITE 278
FT /evidence="ECO:0000305|PubMed:23236156"
FT ACT_SITE 289
FT /evidence="ECO:0000305|PubMed:23236156"
FT ACT_SITE 291
FT /evidence="ECO:0000305|PubMed:23236156"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23236156"
FT BINDING 278
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23236156"
FT MUTAGEN 257
FT /note="E->A: Loss of DNase activity in vitro."
FT /evidence="ECO:0000269|PubMed:23236156"
FT MUTAGEN 278
FT /note="D->A: Loss of DNase activity in vitro and in vivo.
FT Unable to inhibit target cell growth via CDI."
FT /evidence="ECO:0000269|PubMed:23236156"
FT MUTAGEN 322..332
FT /note="KEYALSGRELT->GSG: No longer interacts with cognate
FT CdiI-o11, loss of DNase activity."
FT /evidence="ECO:0000269|PubMed:26449640"
FT MUTAGEN 322..330
FT /note="KEYALSGRE->HTHTLSGEQ: No longer interacts with
FT cognate immunity protein CdiI-o11."
FT /evidence="ECO:0000269|PubMed:26449640"
FT MUTAGEN 323..329
FT /note="EYALSGR->TYSLSGV: Still interacts with cognate
FT immunity protein CdiI-o11."
FT /evidence="ECO:0000269|PubMed:26449640"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:4ZQW"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:4ZQW"
SQ SEQUENCE 377 AA; 40578 MW; D90AB8DC831A6E03 CRC64;
MVNATLSVVQ KNSAFVGSAT GELAARAIGM LYPGVKQSDL SEEQKQTIST LATVSAGLAG
GLTGSSTASA AVGAQSGKNA VENNYLSTNQ SLTFDKELSD CRKSGGNCQD IIDKWEKISD
EQSAEIDQKL KDNPLEAQVI DKEVAKGGYD MTQRPGWLGN IGVEVMTSDE AKAYVQKWNG
RDLTKIDVNS PEWTKFAVFA SDPENQAMLV SGGLLVKDIT KAAISFMSRN TATATVNASE
VGMQWGQGNM KQGMPWEDYV GKSLPADARL PKNFKIFDYY DGATKTATSV KSIDTQTMAK
LANPNQVYSS IKGNIDAAAK FKEYALSGRE LTSSMISNRE IQLAIPADTT KTQWAEINRA
IEYGKSQGVK VTVTQVK
