CDIA_ENTCC
ID CDIA_ENTCC Reviewed; 3321 AA.
AC D5CBA0;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=16S rRNA endonuclease CdiA {ECO:0000305};
DE Short=rRNase CdiA;
DE EC=3.1.-.-;
DE AltName: Full=CdiA-ECL;
DE AltName: Full=Toxin CdiA;
DE Flags: Precursor;
GN Name=cdiA; OrderedLocusNames=ECL_04451;
OS Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC
OS 13535 / NCTC 10005 / WDCM 00083 / NCDC 279-56).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Enterobacter; Enterobacter cloacae complex.
OX NCBI_TaxID=716541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC
RC 279-56;
RX PubMed=20207761; DOI=10.1128/jb.00067-10;
RA Ren Y., Ren Y., Zhou Z., Guo X., Li Y., Feng L., Wang L.;
RT "Complete genome sequence of Enterobacter cloacae subsp. cloacae type
RT strain ATCC 13047.";
RL J. Bacteriol. 192:2463-2464(2010).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC
RC 279-56;
RX PubMed=24889811; DOI=10.1111/mmi.12658;
RA Beck C.M., Diner E.J., Kim J.J., Low D.A., Hayes C.S.;
RT "The F pilus mediates a novel pathway of CDI toxin import.";
RL Mol. Microbiol. 93:276-290(2014).
RN [3]
RP FUNCTION, REQUIRES PMF FOR TRANSLOCATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC
RC 279-56;
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, RECEPTOR FOR ENTRY INTO TARGET CELL CYTOPLASM, AND DOMAIN.
RC STRAIN=ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC
RC 279-56;
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]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 3087-3321 IN COMPLEX WITH CDII,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INDUCTION, DOMAIN, AND MUTAGENESIS
RP OF ASP-3289; ASP-3291; HIS-3293 AND LYS-3300.
RC STRAIN=ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC
RC 279-56;
RX PubMed=24657090; DOI=10.1016/j.str.2014.02.012;
RA Beck C.M., Morse R.P., Cunningham D.A., Iniguez A., Low D.A.,
RA Goulding C.W., Hayes C.S.;
RT "CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into
RT target bacteria.";
RL Structure 22:707-718(2014).
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; upon forced induction decreases E.cloacae target cell counts
CC about 20-fold, about 100-fold in E.coli. Intracellular expression of
CC CdiA-CT (residues 3087-3321) inhibits E.coli cell growth when induced,
CC but coexpression with its cognate immunity protein CdiI allows cell
CC growth. Cleaves 16S rRNA in vivo and in vitro between adenine 1493 and
CC guanosine 1494 of E.coli 16S rRNA. Inhibition of 16S rRNA cleavage is
CC specific to the cognate immunity protein, non-cognate CdiI from
CC E.chrysanthemi strain EC16 does not inhibit this protein
CC (PubMed:24657090). Purified CdiA-CT inhibits E.coli cell growth when
CC added to cultures but not when added as a complex with cognate CdiI,
CC suggesting cognate CdiI prevents import into the target cell. CdiA-CT
CC (without CdiI) is probably imported in an F-pilus-mediated fashion,
CC although it is not clear if this is physiologically significant
CC (PubMed:24889811). Gains access to the cytoplasm of target cells by
CC using integral inner membrane protein FtsH (PubMed:26305955).
CC {ECO:0000269|PubMed:24657090, ECO:0000269|PubMed:24889811,
CC ECO:0000269|PubMed:26305955}.
CC -!- FUNCTION: The CdiA protein is thought to be exported from the cell
CC through the central lumen of CdiB, the other half of its two-partner
CC system (TPS). The TPS domain probably remains associated with CdiB
CC while the FHA-1 domain forms an extended filament with the receptor-
CC binding domain (RBD) at its extremity; in the secretion arrested state
CC the C-terminus of the RBD and YP domains form a hairpin-like structure
CC as the FHA-2, PT and CT domains are periplasmic. The YP domain is
CC probably responsible for this arrest at the point where it re-enters
CC the host cell periplasm. Upon binding to a target cell outer membrane
CC receptor a signal is transmitted to activate secretion. The filament
CC elongates slightly, the rest of CdiA is secreted and the FHA-2 domain
CC becomes stably associated with the target cell's outer membrane where
CC it facilitates entry of the toxic CT domain into the target cell
CC periplasm. From there the toxic CT domain is cleaved and gains access
CC to the target cell cytoplasm via an inner membrane protein (FtsH for
CC this CDI). {ECO:0000305}.
CC -!- SUBUNIT: Interacts with cognate immunity protein CdiI, blocking the
CC active site of the nuclease. {ECO:0000269|PubMed:24657090}.
CC -!- SUBCELLULAR LOCATION: Target cell, target cell cytoplasm
CC {ECO:0000269|PubMed:24657090, ECO:0000269|PubMed:24889811,
CC ECO:0000269|PubMed:25174572}. Note=Secreted to the cell surface by
CC CdiB, its two partner secretion pathway (TPS) partner (Probable). Toxin
CC translocation into the target cell depends on the proton motive force
CC of the target cell, but not on tolA or tonB.
CC {ECO:0000269|PubMed:25174572, ECO:0000305}.
CC -!- INDUCTION: Not expressed under laboratory conditions.
CC {ECO:0000269|PubMed:24657090}.
CC -!- DOMAIN: The 16S rRNASe and CDI activities reside in the C-terminal (CT)
CC domain, residues 3087-3321 (PubMed:24657090, PubMed:24889811). The
CC inner membrane translocation domain (IMTD) targets the toxin to a
CC specific target cell inner membrane protein (FtsH in this case), which
CC delivers the toxin to the target cell cytoplasm (Probable).
CC {ECO:0000269|PubMed:24657090, ECO:0000269|PubMed:24889811,
CC ECO:0000305|PubMed:26305955}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CdiA toxin
CC family. {ECO:0000305}.
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DR EMBL; CP001918; ADF63980.1; -; Genomic_DNA.
DR RefSeq; WP_013098820.1; NC_014121.1.
DR RefSeq; YP_003614929.1; NC_014121.1.
DR PDB; 4NTQ; X-ray; 2.40 A; A=3087-3321.
DR PDBsum; 4NTQ; -.
DR SMR; D5CBA0; -.
DR DIP; DIP-60810N; -.
DR STRING; 716541.ECL_04451; -.
DR EnsemblBacteria; ADF63980; ADF63980; ECL_04451.
DR KEGG; enc:ECL_04451; -.
DR PATRIC; fig|716541.4.peg.4605; -.
DR eggNOG; COG3210; Bacteria.
DR HOGENOM; CLU_000043_2_2_6; -.
DR OMA; NVADANL; -.
DR Proteomes; UP000002363; Chromosome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.160.20.10; -; 1.
DR Gene3D; 3.10.380.20; -; 1.
DR InterPro; IPR010069; CdiA_FHA1_rpt.
DR InterPro; IPR008619; Filamentous_hemagglutn_rpt.
DR InterPro; IPR008638; Filamn_hemagglutn_N.
DR InterPro; IPR025157; Hemagglutinin_rpt.
DR InterPro; IPR028190; Ntox21.
DR InterPro; IPR038181; Ntox21_sf.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR006914; VENN_dom.
DR Pfam; PF05594; Fil_haemagg; 10.
DR Pfam; PF13332; Fil_haemagg_2; 4.
DR Pfam; PF05860; Haemagg_act; 1.
DR Pfam; PF15526; Ntox21; 1.
DR Pfam; PF04829; PT-VENN; 1.
DR SMART; SM00912; Haemagg_act; 1.
DR SUPFAM; SSF51126; SSF51126; 1.
DR TIGRFAMs; TIGR01901; adhes_NPXG; 1.
DR TIGRFAMs; TIGR01731; fil_hemag_20aa; 20.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Nuclease; Signal;
KW Target cell cytoplasm; Toxin; Virulence.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..3321
FT /note="16S rRNA endonuclease CdiA"
FT /evidence="ECO:0000255"
FT /id="PRO_0000432090"
FT REGION 37..323
FT /note="Two-partner system transport domain (TPS)"
FT /evidence="ECO:0000250|UniProtKB:Q3YL96"
FT REGION 332..1496
FT /note="FHA-1"
FT /evidence="ECO:0000305"
FT REGION 430..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1497..1802
FT /note="Receptor binding domain (RBD)"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 1788..1812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1803..1987
FT /note="YP domain"
FT /evidence="ECO:0000250|UniProtKB:Q3YL96"
FT REGION 1837..1875
FT /note="Periplasmic FHA-1 repeat (pFR)"
FT /evidence="ECO:0000305"
FT REGION 1988..2586
FT /note="FHA-2"
FT /evidence="ECO:0000305"
FT REGION 2510..2552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3087..3321
FT /note="CT domain; toxic when added to the outside of
FT E.coli, 16S rRNase activity"
FT /evidence="ECO:0000269|PubMed:24657090,
FT ECO:0000269|PubMed:24889811"
FT REGION 3091..3208
FT /note="Inner membrane translocation domain (IMTD), targets
FT protein to FtsH"
FT /evidence="ECO:0000305|PubMed:26305955"
FT REGION 3174..3236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 3087..3090
FT /note="AENN CT cleavage motif"
FT /evidence="ECO:0000305"
FT COMPBIAS 2516..2552
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3182..3234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 3289
FT /note="D->A: No CDI activity, loss of rRNase, when
FT expressed as isolated CT domain."
FT /evidence="ECO:0000269|PubMed:24657090"
FT MUTAGEN 3291
FT /note="D->A: Delayed CDI activity, reduced rRNase, when
FT expressed as isolated CT domain."
FT /evidence="ECO:0000269|PubMed:24657090"
FT MUTAGEN 3293
FT /note="H->A: No CDI activity, loss of rRNase, when
FT expressed as isolated CT domain in vitro, or in vivo as a
FT fusion with E.coli strain EC93 CdiA."
FT /evidence="ECO:0000269|PubMed:24657090"
FT MUTAGEN 3300
FT /note="K->A: No CDI activity, loss of rRNase, when
FT expressed as isolated CT domain."
FT /evidence="ECO:0000269|PubMed:24657090"
FT HELIX 3250..3256
FT /evidence="ECO:0007829|PDB:4NTQ"
FT TURN 3257..3259
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3262..3264
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3278..3280
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3285..3288
FT /evidence="ECO:0007829|PDB:4NTQ"
FT TURN 3295..3297
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3299..3302
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3306..3312
FT /evidence="ECO:0007829|PDB:4NTQ"
FT STRAND 3318..3320
FT /evidence="ECO:0007829|PDB:4NTQ"
SQ SEQUENCE 3321 AA; 337829 MW; 8705245161CF8846 CRC64;
MMKQDQVRFS QRALSALLSV LLATQPLLPA VAASITPSGN TQMDKAANGV PVVNIATPNQ
SGISHNKYND YNVGKEGLIL NNATGQLNQT QLGGLIQNNP NLKAGQEAKG IINEVTGANR
SNLQGYTEVA GKAANVIVAN PYGITCNGCG FINTPNVTLT TGKPVLDASG KLQSLDVTQG
AVTIEGAGLN GSQSDAVSII SRATEINVQL HAKDLRVVAG ANRVAADGSV SALKGEGTAP
KVAVDTGALG GMYANRIRLV SSETGVGVNL GNLNARQGDI ALSSAGKVVL KNTLASGSTT
VSAADVTLRG DHKAGGNVTV SGQTALTLDQ AHVAADNNLQ LTTRGTLTQN GGAFTAANDA
TLAATTLIQS VDAQASAGRH LAVNAEKNAA LNGSVVAGQQ LSVKGGELVQ QGNLSASEIA
LNAQTLTQES RSTTNASGNI TLTTSGHSQL KGSTTAGQSL AVSAGSLANH GALAAVADTR
INTGIFSNTG TVQGNSLTVS GTDITSSGAL KSASTLDIRA DNATLSGETG AKGKTTVTAS
GNLNNSGTLI SDDTLTLNAA QIVNSGTLSG VRGLTTSGKT FTASATSVTQ SDGDVALNNT
DTTLAGETSA GGAVTVQGRS LNTTATAQTQ GNSVGVAVQN AKLEGTQAAK GNMTLKADSS
LNHTGKSSAS GLKVETGHLS NSGTLTASAL VIDSPEVING GLIHAGQTLS LVTRLLDNRS
SGVLYSPSAL SLSLSELNNA GIITSDAALS LSGSNLTNSG ELSGTSLAID YETLKNSAEG
MLLAQGANRI TAQSVSSAGS MVGNTLTLNA DRLESAGLLQ GDSALSLTAG ILNLLTGSRT
LTGGALGLSG TTLTTAGQLQ GQDVSIRSHD WTNRGSSLAT GSLDVTTAGT LSNTGELMSQ
GNGTLNAVTT VNSGNMLSAG DLSLNGKTLR NSGTLQGNRV TAHQDTITNS GTLTGIAALM
LAARLEMAAP LLTLVNDASG SLLTAGELSV TGGDLRNAGQ WQGKRVLIHA QALTNGGAIQ
AENLLDAQID STLTGTAGSK ITSNGELALS ALTLANSGQW IAKHLTLGAS TLNNSGEITG
VVALSVALTQ LNNQAGGKLL SAGALTLDVE NATNAGQIQG KATTVTAGQL INSGRLQGEA
LTLNASGALN NTASGVLLSE NALTVSTATL NNQGTLQGGG ESSVKATTRV QNDGKMLSGG
KLTLTAPELA NSSSGLVQAV RLLLDVVKAV NGGNVLATTR AELRGSSLDN SGTLQGADLQ
ANYQSVTNSG TVLGTTSLTI NGDALDNTES GKLYSGDKLL LDVRNYSGRG DVVSLGDTTL
KLVNALVNTG TLAASKTLSV SSQNAMTNSG VMQGNAIALS AGGAFTNNGT LTTGNGSSTF
NAQSLLLNAS GSLQAGGDVQ LTSRENITVN GFTGTAGSLT MTAAGTLLNT ALIYAGNNIS
LFAARIHNIY GDILADNSLW MQKNAVGEAN AEVVNRSGTI ETTRGDITVN TGHLLNEADG
LTVSQSEREY PDAIPAADEH YFSYDLNGRR SDFVLLLEDW KNDGSKVVYD WYEQCLGSGA
NGSGQCRDRV DYRLTGEDIR QFLLSESVVS VSATGSSARI AAGRDITINA GTLDNRASHI
LAGRNAVLAG GTLNNLSAEG GRRVTYVQAE YRCEWFYRDC SDSKWEPLTQ YPDGSWGWFD
EDYGWYGWVP YILGERTTEF VADGGVYRSV ISAGGNVSAN FTSDISNTNV TANSGEFSNT
IDAPTLNTLS PEAIGKGLNS ESLAQGGSAD IRFPEQLGNI TDALKDISGG SSLSDQNGSS
GNYPLPSGNN GYFVPSTDPD SPYLITVNPK LDELGNMDDS LFNGLYDLLG ITPGATPRET
NSAYTDRNQF LGSSYFLDRL GLNPDRDYRF LGDAAFDTRY VSNAILNQTG SRYINGIGSD
LDQMRYLMDS AAEQQKTLGL KFGVALTAEQ VAALDKSMLW WESATINGQT VMIPKVYLSP
KDVTVHSGSV ISGNNVQLAG GNVINSGSTI AAQNGLSIDS SNSLSNLNAG LLSAGGGLNL
SALGDINNIG STISGKTVGL ESVAGSINNI TRAQQWNVDA GNVHFSGTDV GKTASITATD
GLTMRAGQDI NVTGANVSAG GSLGMAAGND INITANEIVT SEGRAGRNRA TTETASVTHQ
GSTLSAGDDL TLQAGNDVNA RAAAIAAEGD VGIQAGRDVD LLAEASMERS SSQAKKKTAI
DESVRQQGTE IASGGNTVIL AGRDVTAQAA DVTAQGDIGV AAGRDVNLTT ATESDYRYRE
QTKTSSGFLS KKTTHTIEEE SATREKGSLL SGDNVTVSAG NNLRVLGSAV AGDGDVALSA
GNNVDIVAAT NTDTAWRFKE TKKSGLMGTG GIGFTIGSSK STHDLREQGT TQSESFSTVG
STGGNVSIAA GKQAHIGGAD IIAQKDISLT GDSVVIEPGH DKRTRDEKFE QKSSGLTVAL
SGAAGSAVNN AVTTAQSAKQ SSDSRLAALQ GTQAALSGVQ AGQAVALDQV KGDSDKRNNN
TIGVSASIGS QSSKSSSHME SETTTGSTLS AGNNVTIKAT GSDITVAGSQ IKAGKDVTLD
AARDVNLIAS QDTQQTTGKN SSSGGSLGVG VGVGSGGAGI SISANANSSK GHEKGNGVWQ
NETTVDAGNR VTINTGRDAT IAGAQVSGET VVADIGRDLT IASTQDSDHY NSKQNSVSGG
AGYTFGAGGF SGSINVSRDK MTSDYDSVQE QSGLFAGNGG FDVTVGNHTQ LDSGVIASTA
TADKNRLDTG TLGFSDIHNQ ADFKTEHQGA GISSGGSIGK QFAGNMANAL LAGGGNSGHA
EGTTQAAVSE GTLIIRDKEN QKQDVADLSR DAEHANGSIS PIFDKEKEQQ RLQEVQLIGE
IGSQVVDIAN TQGEINGLNA GRKELADKGI TEPGADASDE VKAAYQNALR ETDAYKTTTA
KYGTGSDLQR GIQAATAALQ GLAGSDLTAA LAGASAPELA YRIGHGMGID NNTAAKTIAH
AILGGAVAAL QGNSAAAGAA GAATGELAAK AIAGMLYPDV KDLSTLSEEQ KQTVSALATI
SAGMAGGLAG DSTGSAVAGG QAGKNAAENN SLALVARGCA VAAPCRTKVA EQLLEIGAKA
GIAGLAGAAV KDMADKMTSD ELEHLVTLEM MGNDEIIAKY VSLLHDKYAP SHTGGNLLPE
TLPGHTGNNT GSVDTGPNHT GNTNRQNDSG SNNTGNTEGA PNTGGNTTIT PIPNGPSKDD
IAYLALKGKE AQEAASNLGF DRRIPPQKAP FNSHGQPVFY DGKNYITPDI DSHNVTNGWK
MFNSKGKRIG TYDSGLNRIK D
