CDIA_ECONC
ID CDIA_ECONC Reviewed; 3289 AA.
AC P0DSI1;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 25-MAY-2022, entry version 11.
DE RecName: Full=tRNA nuclease CdiA {ECO:0000303|PubMed:28973472};
DE Short=tRNase CdiA;
DE EC=3.1.-.- {ECO:0000269|PubMed:28973472};
DE AltName: Full=CdiA-NC101 {ECO:0000303|PubMed:26305955};
DE AltName: Full=Toxin CdiA;
DE Flags: Precursor;
GN Name=cdiA {ECO:0000303|PubMed:28973472}; ORFNames=ECNC101_09164;
OS Escherichia coli (strain NC101).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=753642;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NC101;
RA Suzuki H., Richards V., Lefebure T., Pavinski Bitar P., Lang P.,
RA Stanhope M.;
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, RECEPTOR FOR ENTRY INTO TARGET CELL CYTOPLASM, AND DOMAIN.
RC STRAIN=NC101;
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=NC101;
RX PubMed=28223500; DOI=10.1073/pnas.1619273114;
RA Jones A.M., Garza-Sanchez F., So J., Hayes C.S., Low D.A.;
RT "Activation of contact-dependent antibacterial tRNase toxins by translation
RT elongation factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E1951-E1957(2017).
RN [4] {ECO:0007744|PDB:5I4Q, ECO:0007744|PDB:5I4R}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 3197-3288 IN COMPLEX WITH GDP;
RP EF-TU AND CDII-NC101, FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF
RP TYR-3226; GLN-3232; ARG-3234; GLU-3270; HIS-3282 AND GLN-3284.
RC STRAIN=NC101;
RX PubMed=28973472; DOI=10.1093/nar/gkx700;
RA Michalska K., Gucinski G.C., Garza-Sanchez F., Johnson P.M., Stols L.M.,
RA Eschenfeldt W.H., Babnigg G., Low D.A., Goulding C.W., Joachimiak A.,
RA Hayes C.S.;
RT "Structure of a novel antibacterial toxin that exploits elongation factor
RT Tu to cleave specific transfer RNAs.";
RL Nucleic Acids Res. 45:10306-10320(2017).
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 (target cell counts decrease about 10,0000-fold for this
CC system). CdiA toxicity is neutralized by its cognate immunity protein
CC CdiI-NC101, but not by CdiI from other bacteria (PubMed:26305955,
CC PubMed:28973472). The C-terminal domain (CT) cleaves tRNA
CC endonucleolytically at the 5' side of guanine discriminator nucleotide
CC sites (removes the last 4 nucleotides of the tRNA acceptor arm when the
CC first nucleotide to be removed is G) (PubMed:28973472). Requires EF-Ts
CC (tsf) for toxic function of the CT domain in vivo (PubMed:28223500). In
CC vitro the CT tRNase activity requires both EF-Tu (tufA) and EF-Ts. EF-
CC Ts probably increases steady-state GTP-EF-Tu-aa-tRNA substrate levels.
CC The CT domain is thought to remodel this same complex to displace the
CC 3'-end of the aa-tRNA and allow it to enter into the toxin active site
CC (PubMed:28973472). The CT domain gains access to the cytoplasm of
CC target cells by using integral inner membrane protein PTS system
CC glucose-specific EIICB component (ptsG) (PubMed:26305955).
CC {ECO:0000269|PubMed:26305955, ECO:0000269|PubMed:28223500,
CC ECO:0000269|PubMed:28973472}.
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 (PtsG for
CC this CDI). {ECO:0000305|PubMed:26305955}.
CC -!- SUBUNIT: Forms a contact-dependent growth inhibition complex of CdiA-
CC CT-NC101, CdiI-NC101 and EF-Tu; the complex is a dimer of
CC heterotrimers. Stable CdiA-CT-NC101, EF-Tu complexes are not detected,
CC nor are complexes with EF-Ts. {ECO:0000269|PubMed:28973472}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Target cell, target cell
CC cytoplasm {ECO:0000269|PubMed:28973472}. Note=Secreted to the cell
CC surface by CdiB, its two partner secretion pathway (TPS) partner.
CC {ECO:0000305}.
CC -!- DOMAIN: The C-terminal domain (CT) has toxic tRNase activity.
CC {ECO:0000269|PubMed:28973472}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CdiA toxin
CC family. {ECO:0000305}.
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DR EMBL; AEFA01000002; EFM55009.1; -; Genomic_DNA.
DR RefSeq; WP_000554167.1; NZ_AEFA01000002.1.
DR PDB; 5I4Q; X-ray; 2.35 A; A=3197-3288.
DR PDB; 5I4R; X-ray; 3.30 A; A/E=3197-3288.
DR PDBsum; 5I4Q; -.
DR PDBsum; 5I4R; -.
DR SMR; P0DSI1; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.160.20.10; -; 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; IPR006626; PbH1.
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; PF04829; PT-VENN; 1.
DR SMART; SM00912; Haemagg_act; 1.
DR SMART; SM00710; PbH1; 7.
DR SUPFAM; SSF51126; SSF51126; 1.
DR TIGRFAMs; TIGR01901; adhes_NPXG; 1.
DR TIGRFAMs; TIGR01731; fil_hemag_20aa; 22.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Nuclease; Secreted; Signal;
KW Target cell cytoplasm; Toxin; Virulence.
FT SIGNAL 1..32
FT /evidence="ECO:0000305"
FT CHAIN 33..3289
FT /note="tRNA nuclease CdiA"
FT /id="PRO_0000447223"
FT REGION 36..322
FT /note="Two-partner system transport domain (TPS)"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 351..1398
FT /note="FHA-1"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 595..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1399..1689
FT /note="Receptor binding domain (RBD)"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 1690..1874
FT /note="YP domain"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 1875..1935
FT /note="Periplasmic FHA-1 repeat (pFR)"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 1979..2653
FT /note="FHA-2"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 2097..2116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2332..2356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2466..2513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2992..3034
FT /note="Pretoxin (PT) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 3035..3289
FT /note="C-terminal effector domain (CT); has tRNase
FT activity"
FT /evidence="ECO:0000269|PubMed:28973472"
FT REGION 3039..3197
FT /note="Inner membrane translocation domain (IMTD), targets
FT protein to PtsG"
FT /evidence="ECO:0000305|PubMed:26305955"
FT MOTIF 3035..3038
FT /note="VENN CT cleavage motif"
FT /evidence="ECO:0000305"
FT COMPBIAS 2468..2511
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 3226
FT /note="Y->A: No cleavage of tRNA in vivo or in vitro, has
FT no CDI activity in vivo. No longer interacts with EF-Tu."
FT /evidence="ECO:0000269|PubMed:28973472"
FT MUTAGEN 3232
FT /note="Q->A: Full cleavage of tRNA in vivo, has wild-type
FT CDI activity in vivo."
FT /evidence="ECO:0000269|PubMed:28973472"
FT MUTAGEN 3234
FT /note="R->A: No cleavage of tRNA in vivo, has no CDI
FT activity in vivo."
FT /evidence="ECO:0000269|PubMed:28973472"
FT MUTAGEN 3270
FT /note="E->A: Nearly complete cleavage of tRNA in vivo,
FT attenuated CDI activity in vivo."
FT /evidence="ECO:0000269|PubMed:28973472"
FT MUTAGEN 3282
FT /note="H->A: No cleavage of tRNA in vivo or in vitro, has
FT no CDI activity in vivo."
FT /evidence="ECO:0000269|PubMed:28973472"
FT MUTAGEN 3284
FT /note="Q->A: Full cleavage of tRNA in vivo, has wild-type
FT CDI activity in vivo."
FT /evidence="ECO:0000269|PubMed:28973472"
FT STRAND 3211..3216
FT /evidence="ECO:0007829|PDB:5I4Q"
FT STRAND 3219..3222
FT /evidence="ECO:0007829|PDB:5I4Q"
FT HELIX 3223..3231
FT /evidence="ECO:0007829|PDB:5I4Q"
FT HELIX 3237..3245
FT /evidence="ECO:0007829|PDB:5I4Q"
FT STRAND 3250..3253
FT /evidence="ECO:0007829|PDB:5I4Q"
FT STRAND 3262..3266
FT /evidence="ECO:0007829|PDB:5I4Q"
FT STRAND 3269..3274
FT /evidence="ECO:0007829|PDB:5I4Q"
FT TURN 3275..3278
FT /evidence="ECO:0007829|PDB:5I4Q"
FT STRAND 3279..3285
FT /evidence="ECO:0007829|PDB:5I4Q"
SQ SEQUENCE 3289 AA; 336592 MW; 7E568D6C044DAD64 CRC64;
MHQPPVRFTY RLLSYLISTI IAGQPLLPAV GAVITPQNGA GMDKAANGVP VVNIATPDGA
GISHNRFTDY NVGKEGLILN NATGKLNPTQ LGGLIQNNPN LKAGGEAKGI INEVTGGNRS
LLQGYTEVAG KAANVMVANP YGITCDGCGF INTPHATLTT GRPVMNADGS LQALEVTEGS
ITINGAGLDG TRSDAVSIIA RATEVNAALH AKDLTVTAGA NRITADGRVS ALKGEGDVPK
VAVDTGALGG MYARRIHLTS TESGVGVNLG NLYARDGDIT LDASGRLTVN NSLATGAVTA
KGQGVTLTGD HKAGGNLSVS SRSDIVLSNG TLNSDKDLSL TAGGRITQQN EKLTAGRDVT
LAAKNITQDT ASQINAARDI VTVSSDTLTT QGQITAGQNL TASATTLTQD GTLLAKGHAG
LDAGTLNNSG AVQGASLTLG STTLSNSGSL LSGGPLTVNT RDFTQSGRTG AKGKVDITAS
GKLTSTGSLV SDDVLVLKAQ DVTQNGVLSG GKGLTVSAQA LSSGKKSVTH SDAAMTLNVT
TVALDGENSA GDTLRVQADK LSTAAGAQLQ SGKNLSINAR DARLAGTQAA QQTMAVNASE
KLTHSGKSSA PSLSLSAPEL TSSGVLVGSA LNTQSQTLTN SGLLQGEASL TVNTQRLDNQ
QNGTLYSAAD LTLDIPDIRN SGLITGDNGL TLNTASLSNP GKIIADTLNV RATTLDGDGL
LQGAGALALA GDTLSQGRNG RWLTAGDLSL RGKTLHTAGT TQGQNLTVQA DNWANSGSVL
ATGNLTASAT GQLTSTGDIM SQGDTTLNAA TTDNRGSLLS AGTLSLDGNS LDNRGTVQGN
HVTIRQNSVT NSGTLTGIAA LTLAARMDMA SPQPALMNNG GSLLTSGDLT ITAGSITSSG
HWQGKQVLIT ADSLANSGAI QAADSLTARL TGELVSTAGS KVTSNGEMAL SALNLSNSGQ
WIAKNLTLKA NSLTSAGDIT GVDALTLTVN QTLNNHASGK LLSAGVLTLK ADSVKNDGQL
QGNATTITAG QLTNGGHLQG ETLTLTASGG VNNRSGGVLM SRNALNVSTA TLSNQGTIQG
GGGVSLNATD RLQNDGKILS GSNLTLTAQV LANTGSGLVQ AATLLLDVVN TVNGGRVLAT
GSADVKGTTL NNTGTLQGAD LLVNYHTFSN SGTLLGTSGL GVKGSSLLQN GTGRLYSAGN
LLLDAQDFSG QGQVVATGDV TLKLIAALTN HGTLAAGKTL SVTSQNAITN GGVMQGDAMV
LGAGEAFTNN GMLTAGKGNS VFSAQRLFLN APGSLQAGGD VSLNSRSDIT ISGFTGTAGS
LTMNVAGTLL NSALIYAGNN LKLFTDRLHN QHGDILAGNS LWVQKDASGG ANTEIINTSG
NIETHQGDIV VRTGHLLNQR EGFSATTTTR TNPSSIQGMG NALVDIPLSL LPDGSYGYFT
REVENQHGTP CNGHGACNIT MDTLYYYAPF ADSATQRFLS SQNITTVTGA DNPAGRIASG
RNLSAEAERL ENRASFILAN GDIALSGREL SNQSWQTGTE NEYLVYRYDP KTFYGSYATG
SLDKLPLLSP EFENNTIRFS LDGREKDYTP GKTYYSVIQA GGDVKTRFTS SINNGTTTAH
AGSVSPVVSA PVLNTLSQQT GGDSLTQTAL QQYEPVVVGS PQWHDELAGA LKNIAGGSPL
TGQTGISDDW PLPSGNNGYL VPSTDPDSPY LITVNPKLDG LGQVDSHLFA GLYELLGAKP
GQAPRETAPS YTDEKQFLGS SYFLDRLGLK PEKDYRFLGD AVFDTRYVSN AVLSRTGSRY
LNGLGSDTEQ MRYLMDNAAR QQKGLGLEFG VALTAEQIAQ LDGSILWWES ATINGQTVMV
PKLYLSPEDI TLHNGSVISG NNVQLAGGNI TNSGGSINAQ NGLSLDSTGY IDNLNAGLIS
AGGSLDLSAI GDISNISSVI SGKTVQLESV SGNISNITRR QQWNAGSDSR YGGVHLSGTD
TGPVATIKGT DSLSLDAGKN IDITGATVSS GGTLGMSAGN DINIAANLIS GSKSQSGFWH
TDDNSASSTT SQGSSISAGG NLAMAAGHNL DVTASSVSAG HSALLSAGND LSLNAVRESK
NSRNGRSESH ESHAAVSTVT AGDNLLLVAG RDVASQAAGV AAENNVVIRG GRDVNLVAES
AGAGDSYTSK KKKEINETVR QQGTEIASGG DTTVNAGRDI TAVASSVTAT GNISVNAGRD
VALTTATESD YHYLETKKKS GGFLSKKTTH TISEDSASRE AGSLLSGNRV TVNAGDNLTV
EGSDVVADQD VSLAAGNHVD VLAATSTDTS WRFKETKKSG LMGTGGIGFT IGSSKTTHDR
REAGTTQSQS ASTIGSTAGN VSITAGKQAH ISGSDVIANR DISITGDSVV VDPGHDRRTV
DEKFEQKKSG LTVALSGTVG SAINNAVTSA QETKESSDSR LKALQATKTA LSGVQAGQAA
AMATATGDPN ATGVSLSLTT QKSKSQQHSE SDTVSGSTLN AGNNLSVVAT GKNRGDNRGD
IVIAGSQLKA GGNTSLDAAN DVLLSGAANT QKTTGRNSSS GGGVGVSIGA GGNGAGISVF
ASVNAAKGSE KGNGTEWTET TIDSGKTVTI NSGRDTVLNG AQVNGNRIIA DVGHDLLISS
QQDTSKYDSK QTSVAAGGSF TFGSMTGSGY IAASRDKMKS RFDSVAEQTG MFSGDGGFDI
TVGNHTQLDG AVIASTATAD KNSLDTGTLG FSDIHNEADY KVSHSGISLS GGGSFGDKFQ
GNMPGGMISA GGHSGHAEGT TQAAVADGTI TIRDRDNQKQ NLANLSRDPA HANDSISPIF
DKEKEQRRLQ TVGLISDIGS QVADIARTQG ELNALKAAQD KYGPVPADAT EEQRQAYLAK
LRDTPEYKKE QEKYGTGSEI QRGIQAATAA LQGLAGGNLA GALAGASAPE LAHLLKSTEK
DPAVNAIAHA ILGGTVAAMQ GNNVAAGAAG AATGELAARA IAGMLYPGVK QSDLSEEQKQ
TISTLATVSA GLAGGLTGNS TASAAVGAQS GKNAVENNYL SVSEKTELEI AKQTLKNSKD
PAEREKAQQK YDALLEKDIA SDKEVIAACS NGNASSSACA SARLKVIASK EGYEDGPYNS
KYSQQYADAY GQIVNLLDIT SVDAQNQQQV KNAMINYFMV TKGVDRQTAE SYTETTQGLE
IIAASVTPLI GQAASNKLSY LGIGKKISFD GDFYTVDGMK FSKSYYEKLW EQGRPAPFVQ
AREVLNSNPK IEPDPRGAPG YLRYEGAGLE MIYNPKTGQV GHIQPVKVK
