CDIA9_BURPE
ID CDIA9_BURPE Reviewed; 1307 AA.
AC H9T8G6;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 25-MAY-2022, entry version 23.
DE RecName: Full=tRNA nuclease CdiA;
DE EC=3.1.-.-;
DE AltName: Full=CdiA-E479 {ECO:0000303|PubMed:22435733};
DE AltName: Full=Toxin CdiA;
DE Flags: Fragment;
GN Name=cdiA;
OS Burkholderia pseudomallei (Pseudomonas pseudomallei).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Burkholderia; pseudomallei group.
OX NCBI_TaxID=28450;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=E479;
RX PubMed=18299706; DOI=10.1371/journal.pntd.0000182;
RA Chantratita N., Wuthiekanun V., Limmathurotsakul D., Vesaratchavest M.,
RA Thanwisai A., Amornchai P., Tumapa S., Feil E.J., Day N.P., Peacock S.J.;
RT "Genetic diversity and microevolution of Burkholderia pseudomallei in the
RT environment.";
RL PLoS Negl. Trop. Dis. 2:E182-E182(2008).
RN [2]
RP FUNCTION, INTERACTION WITH CDII, SUBUNIT, DOMAIN, EXPRESSION IN E.COLI, AND
RP MUTAGENESIS OF ASP-1271 AND ASP-1276.
RC STRAIN=E479;
RX PubMed=22435733; DOI=10.1111/j.1365-2958.2012.08039.x;
RA Nikolakakis K., Amber S., Wilbur J.S., Diner E.J., Aoki S.K., Poole S.J.,
RA Tuanyok A., Keim P.S., Peacock S., Hayes C.S., Low D.A.;
RT "The toxin/immunity network of Burkholderia pseudomallei contact-dependent
RT growth inhibition (CDI) systems.";
RL Mol. Microbiol. 84:516-529(2012).
RN [3] {ECO:0007744|PDB:5J4A}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1147-1307 IN COMPLEX WITH CDII,
RP FUNCTION, POSSIBLE ACTIVE SITE, SUBUNIT, TRNA-BINDING, AND MUTAGENESIS OF
RP GLU-1195; ASP-1220; ASP-1234; HIS-1266 AND ASP-1276.
RC STRAIN=E479;
RX PubMed=27445337; DOI=10.1074/jbc.m116.736074;
RA Johnson P.M., Gucinski G.C., Garza-Sanchez F., Wong T., Hung L.W.,
RA Hayes C.S., Goulding C.W.;
RT "Functional diversity of cytotoxic tRNase/immunity protein complexes from
RT Burkholderia pseudomallei.";
RL J. Biol. Chem. 291:19387-19400(2016).
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. The C-terminal 160 residues (CT domain) acts as a general tRNA
CC nuclease, and inhibits growth in E.coli upon overexpression. Cleaves
CC specifically within the T-loop of E.coli tRNA2(Arg) (between the post-
CC transcriptionally modified thymidine-T55 and pseudouridine-Y56); also
CC degrades most other tRNAs (PubMed:22435733). Cleaves unmodified
CC tRNA(Gln) and tRNA(Asp), showing the universal post-translational tRNA
CC modifications present in the T-loop are not required for CT activity
CC (PubMed:27445337). Inactive CT domain binds tRNA, probably in a complex
CC with 4 CT domains and 4 tRNAs (PubMed:27445337). Toxic activity is
CC neutralized by coexpression of the cognate immunity protein CdiI in
CC E.coli, but not by non-cognate immunity proteins from other strains of
CC B.pseudomallei (PubMed:22435733, PubMed:27445337).
CC {ECO:0000269|PubMed:22435733, ECO:0000269|PubMed:27445337}.
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 domain form a hairpin-like structure as the
CC FHA-2, PT and CT domains are periplasmic. Upon binding to a target cell
CC outer membrane receptor a signal is transmitted to activate secretion.
CC The filament elongates slightly, the rest of CdiA is secreted and the
CC FHA-2 domain becomes stably associated with the target cell's outer
CC membrane where it facilitates entry of the toxic CT domain into the
CC target cell periplasm. From there the toxic CT domain is cleaved and
CC gains access to the target cell cytoplasm via an inner membrane
CC protein. {ECO:0000250|UniProtKB:A0A1S4NYE3,
CC ECO:0000250|UniProtKB:I1WVY3}.
CC -!- SUBUNIT: Specifically interacts with cognate immunity protein CdiI,
CC which blocks its tRNA nuclease activity (PubMed:22435733,
CC PubMed:27445337). The CT domain forms a tetramer both with and without
CC tRNA; each subunit binds tRNA in its presence (PubMed:27445337).
CC {ECO:0000269|PubMed:22435733, ECO:0000269|PubMed:27445337}.
CC -!- SUBCELLULAR LOCATION: Target cell, target cell cytoplasm
CC {ECO:0000250|UniProtKB:I1WVY3}. Note=Secreted to the cell surface by
CC CdiB, its two partner secretion pathway (TPS) partner.
CC {ECO:0000250|UniProtKB:I1WVY3}.
CC -!- DOMAIN: The C-terminal domain (CT) has toxic activity, which can be
CC exchanged between N-terminal sections from different toxin molecules.
CC {ECO:0000269|PubMed:22435733}.
CC -!- SIMILARITY: Belongs to the CdiA toxin family. {ECO:0000305}.
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DR EMBL; JQ423914; AFG17280.1; -; Genomic_DNA.
DR PDB; 5J4A; X-ray; 2.00 A; A/C=1148-1307.
DR PDBsum; 5J4A; -.
DR AlphaFoldDB; H9T8G6; -.
DR SMR; H9T8G6; -.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR InterPro; IPR041620; CdiA_C_tRNase.
DR InterPro; IPR025157; Hemagglutinin_rpt.
DR Pfam; PF18664; CdiA_C_tRNase; 1.
DR Pfam; PF13332; Fil_haemagg_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Nuclease; RNA-binding;
KW Target cell cytoplasm; Toxin; tRNA-binding; Virulence.
FT CHAIN <1..1307
FT /note="tRNA nuclease CdiA"
FT /id="PRO_0000429693"
FT REGION <1..251
FT /note="FHA-2"
FT /evidence="ECO:0000305"
FT REGION 252..991
FT /note="Pretoxin (PT) domain"
FT /evidence="ECO:0000305"
FT REGION 317..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 996..1193
FT /note="Probable inner membrane translocation domain"
FT /evidence="ECO:0000305|PubMed:27445337"
FT REGION 1124..1164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1147..1307
FT /note="C-terminal effector domain (CT), has tRNA nuclease
FT activity"
FT /evidence="ECO:0000269|PubMed:22435733"
FT MOTIF 992..995
FT /note="ELYN C-terminal motif"
FT /evidence="ECO:0000305|PubMed:22435733"
FT COMPBIAS 492..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1195
FT /evidence="ECO:0000305|PubMed:27445337"
FT ACT_SITE 1220
FT /evidence="ECO:0000305|PubMed:27445337"
FT ACT_SITE 1234
FT /evidence="ECO:0000305|PubMed:27445337"
FT ACT_SITE 1266
FT /evidence="ECO:0000305|PubMed:27445337"
FT MUTAGEN 1195
FT /note="E->A: Protein not toxic in E.coli, CT domain has no
FT tRNase activity, still interacts with cognate CdiI."
FT /evidence="ECO:0000269|PubMed:27445337"
FT MUTAGEN 1220
FT /note="D->A: Protein not toxic in E.coli, CT domain has no
FT tRNase activity, still interacts with cognate CdiI."
FT /evidence="ECO:0000269|PubMed:27445337"
FT MUTAGEN 1234
FT /note="D->A: Protein not toxic in E.coli, CT domain has no
FT tRNase activity, still interacts with cognate CdiI, CT
FT fragment still binds tRNA."
FT /evidence="ECO:0000269|PubMed:27445337"
FT MUTAGEN 1266
FT /note="H->A: Protein not toxic in E.coli, CT domain has no
FT tRNase activity, still interacts with cognate CdiI."
FT /evidence="ECO:0000269|PubMed:27445337"
FT MUTAGEN 1271
FT /note="D->A: CT domain not toxic in E.coli."
FT /evidence="ECO:0000269|PubMed:22435733"
FT MUTAGEN 1276
FT /note="D->A: CT domain not toxic in E.coli, CT domain has
FT no tRNase activity."
FT /evidence="ECO:0000269|PubMed:22435733,
FT ECO:0000305|PubMed:27445337"
FT NON_TER 1
FT HELIX 1193..1206
FT /evidence="ECO:0007829|PDB:5J4A"
FT STRAND 1210..1212
FT /evidence="ECO:0007829|PDB:5J4A"
FT STRAND 1218..1223
FT /evidence="ECO:0007829|PDB:5J4A"
FT TURN 1227..1230
FT /evidence="ECO:0007829|PDB:5J4A"
FT HELIX 1242..1269
FT /evidence="ECO:0007829|PDB:5J4A"
FT STRAND 1270..1275
FT /evidence="ECO:0007829|PDB:5J4A"
FT HELIX 1277..1279
FT /evidence="ECO:0007829|PDB:5J4A"
FT HELIX 1282..1292
FT /evidence="ECO:0007829|PDB:5J4A"
FT HELIX 1297..1300
FT /evidence="ECO:0007829|PDB:5J4A"
FT STRAND 1303..1305
FT /evidence="ECO:0007829|PDB:5J4A"
SQ SEQUENCE 1307 AA; 128934 MW; B78B7F6B5D824C9E CRC64;
SLDTTGNVDL TSANVKAGSL DLNAGNKLIL DTATQTTHQV SRDGATSDKT TLGPAANLNV
AGDASIKTGG DFQQNAGNLN VGGNLNANIG GNWNLGVQQT GEHKVVQRAN GVSDTDLNSA
TGSTVNVGGK SAIGVGGDLT AQGARLDFGQ GGTVAAKGNV TFGAASTTST INANSSGDQG
NRSYAETRHG ADQALTGTTV KGGDTLNVVS GKDINVIGST IDLKKGDANL LAAGDVNVGA
ATETHVYNSR ETHSRSGVVS GTKIASSQDA TSTVANGSLI SADGVSIGSG KDINVQGSTV
VGTHDVALNA AHDVNITTSQ DTSQSSTTYQ EQHSGLMSGG GLSFSVGNSK LAQQNQSSSV
TNNASTVGSV DGNLTVNAGN TLHVKGSDLV AGKDVTGTAA NIVVDSATDT THQAQQQQTS
KSGLTVGLSG SVGDAINNAI SETQAARESA KDSNGRASAL HSIAAAGDVA FGGLGAKALL
DGAKGPQAPS IGVQVSVGSS HSSMQSSEDQ TIQRGSSINA GGNAKLIATG NGTPKDGNIT
IAGSNVNAAN VALVANNQVN LVNTTDTDKT QSSNSSSGSS VGVSIGTNGI GVSASMQRAH
GDGNSDAAIQ NNTHINASQT ATIVSGGDTN VIGANVNANK VVADVGGNLN VASVQDTTVS
AAHQSSAGGG FTISQTGGGA SFSAQNGHAD GNYAGVKEQA GIQAGSGGFD VTVKGNTDLK
GAYIGSTADA SKNSLTTGTL TTSDIENHSH YSANSAGFSA GASVGVSTKA VGPSSVSGSG
GVTPMVFQND SGDQSATTKS AVSVGAINIT KPGEQTQDVA NLNRDATNLN GTVSKTPDVQ
KMLSQQADTM NAAQAAGQTV SQGIGLYADG KRKDAIDAAK AAYERGDLVA MQSYIDQAKS
WDEGGASRAG LQATGGALIG GLGGGSVLTA IGGAAGAGTS SLLAGQAEKI SKSVGDMTGS
SLVGNIAANV AATVGGALVG GSAGAAMASN VELYNAGNDP QKTDDRATIA GLQGLLSRTA
AMASDAKAGV WNGMVNVAGV IVNIPNGGPF ASPGDPGYVS LDGLKKPYKS GTSIGPDTEF
LTPILATLGL GGKAAVGTDA GITSADVATV GNGALKNASG DLSAAANSAR NQPYGQGASA
SQSPGTQGAS SGSNISASNG SSSPTTIVAS NPVDLNAFDR LNVVDPAVGK FRPGEAGAAA
ELENYLGGTL QRAPQGSSVD FVFSSGPNNG KTVDFMLTPD TVAQAAKINQ FFDKNLNNFM
NTLSDHAAAA DFVPLDSRFL SEANKTLLVK AIGNLPQKLQ AKIILIK
