CDIA2_BURP2
ID CDIA2_BURP2 Reviewed; 3122 AA.
AC I1WVY3;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=tRNA nuclease CdiA-2;
DE Short=tRNase CdiA-2;
DE EC=3.1.-.- {ECO:0000269|PubMed:22435733};
DE AltName: Full=CdiA-Bp1026b {ECO:0000303|PubMed:22435733};
DE AltName: Full=Toxin CdiA-2;
DE AltName: Full=Toxin CdiA-II;
GN Name=cdiA2; OrderedLocusNames=BP1026B_II2207;
OS Burkholderia pseudomallei (strain 1026b).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Burkholderia; pseudomallei group.
OX NCBI_TaxID=884204;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=1026b;
RX PubMed=22615773; DOI=10.1371/journal.pone.0036507;
RA Hayden H.S., Lim R., Brittnacher M.J., Sims E.H., Ramage E.R., Fong C.,
RA Wu Z., Crist E., Chang J., Zhou Y., Radey M., Rohmer L., Haugen E.,
RA Gillett W., Wuthiekanun V., Peacock S.J., Kaul R., Miller S.I., Manoil C.,
RA Jacobs M.A.;
RT "Evolution of Burkholderia pseudomallei in recurrent melioidosis.";
RL PLoS ONE 7:E36507-E36507(2012).
RN [2]
RP FUNCTION, INTERACTION WITH CDII, SUBUNIT, EXPRESSION IN E.COLI, DOMAIN, AND
RP MUTAGENESIS OF ASP-3039.
RC STRAIN=1026b;
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]
RP FUNCTION, REQUIRES PMF FOR TRANSLOCATION, AND SUBCELLULAR LOCATION.
RC STRAIN=1026b;
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 IDENTIFICATION OF POSSIBLE RECEPTORS.
RX PubMed=25786241; DOI=10.1371/journal.pone.0120265;
RA Koskiniemi S., Garza-Sanchez F., Edman N., Chaudhuri S., Poole S.J.,
RA Manoil C., Hayes C.S., Low D.A.;
RT "Genetic analysis of the CDI pathway from Burkholderia pseudomallei
RT 1026b.";
RL PLoS ONE 10:E0120265-E0120265(2015).
RN [5]
RP FUNCTION, AND DOMAIN.
RC STRAIN=1026b;
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 [6]
RP FUNCTION, POSSIBLE ACTIVE SITE, TRNA-BINDING, AND MUTAGENESIS OF ASP-3039.
RC STRAIN=1026b;
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 2948-3122 IN COMPLEX WITH CDII,
RP FUNCTION, POSSIBLE ACTIVE SITE, AND SUBUNIT.
RC STRAIN=1026b;
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).
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 301 residues (the CT fragment) cleaves near the
CC C-terminus of E.coli tRNA1B(Ala), probably preventing tRNA charging,
CC and inhibits growth in E.coli. A truncated CT fragment (residues 2948-
CC 3122) has tRNA endonuclease activity on several B.thailandensis tRNAs
CC as well as tRNA2(Arg) where it cleaves after A-70 and U-71
CC (PubMed:22435733, PubMed:25174572). Inactive CT domain binds tRNA,
CC probably in a 1:1 complex (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:23236156). May use
CC lipopolysaccharide as its target cell receptor (PubMed:25786241).
CC Probably gains access to the cytoplasm of target cells (B.thailandensis
CC strain E264) by using integral inner membrane protein BTH_II0599
CC (PubMed:25786241, PubMed:26305955). Protein BTH_I0359 is also
CC implicated in an unknown fashion in CDI in B.thailandensis strain E264
CC (PubMed:25786241). {ECO:0000269|PubMed:22435733,
CC ECO:0000269|PubMed:23236156, ECO:0000269|PubMed:25174572,
CC ECO:0000269|PubMed:25786241, ECO:0000269|PubMed:26305955,
CC ECO:0000269|PubMed:27445337}.
CC -!- FUNCTION: Expression of this cdiAIB locus in B.thailandensis confers
CC protection against other bacteria carrying the locus; growth inhibition
CC requires cellular contact. {ECO:0000269|PubMed:22435733}.
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 (possibly a lipoprotein in this CDI) a signal
CC is transmitted to activate secretion. The filament elongates slightly,
CC the rest of CdiA is secreted and the FHA-2 domain becomes stably
CC associated with the target cell's outer membrane where it facilitates
CC entry of the toxic CT domain into the target cell periplasm. From there
CC the toxic CT domain is cleaved and gains access to the target cell
CC cytoplasm via an inner membrane protein (probably inner membrane
CC protein BTH_II0599). {ECO:0000250|UniProtKB:A0A1S4NYE3,
CC ECO:0000305|PubMed:25786241, ECO:0000305|PubMed:26305955}.
CC -!- SUBUNIT: Interacts with cognate immunity protein CdiI, which blocks its
CC tRNA nuclease activity (Probable). The truncated CT fragment (residues
CC 2948-3122) specifically interacts with cognate CdiI which inhibits the
CC tRNA nuclease activity. The truncated CT is more stable in vitro than
CC the original CT fragment characterized in E.coli.
CC {ECO:0000269|PubMed:22435733, ECO:0000269|PubMed:23236156,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Secreted {ECO:0000305|PubMed:25174572}. Target
CC cell, target cell cytoplasm {ECO:0000305|PubMed:25174572}.
CC Note=Secreted to the cell surface by CdiB, its two partner secretion
CC pathway (TPS) partner (Probable). Probably translocated into the target
CC cell cytoplasm as intracellular CdiI inhibits tRNase activity. Toxin
CC translocation into the target cell depends on the proton motive force
CC (pmf) of the target cell, but not on tolA or tonB. The pmf is probably
CC required for translocation across the target cell inner membrane from
CC its periplasm. {ECO:0000269|PubMed:25174572, ECO:0000305}.
CC -!- DOMAIN: The C-terminal domain (CT) has toxic activity, which can be
CC exchanged between N-terminal sections from different toxin molecules
CC (PubMed:22435733, PubMed:25174572). A subdomain of the CT has tRNase
CC activity and can be targeted to usually non-susceptible bacteria by
CC cloning. Exchanging this toxic domain between CdiA proteins alters the
CC inner membrane protein delivery system but not the CdiI immunity
CC protein, strongly suggesting CdiI recognizes only the toxic domain
CC (PubMed:26305955). {ECO:0000269|PubMed:22435733,
CC ECO:0000269|PubMed:25174572, ECO:0000269|PubMed:26305955}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CdiA toxin
CC family. {ECO:0000305}.
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DR EMBL; CP002834; AFI70427.1; -; Genomic_DNA.
DR RefSeq; WP_004553664.1; NZ_CP004380.1.
DR PDB; 4G6V; X-ray; 2.64 A; A/C/E/G=2948-3122.
DR PDBsum; 4G6V; -.
DR SMR; I1WVY3; -.
DR EnsemblBacteria; AFI70427; AFI70427; BP1026B_II2207.
DR KEGG; bpz:BP1026B_II2207; -.
DR PATRIC; fig|884204.3.peg.6693; -.
DR Proteomes; UP000010087; Chromosome 2.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004549; F:tRNA-specific ribonuclease activity; IDA:UniProtKB.
DR CDD; cd13442; CDI_toxin_Bp1026b_like; 1.
DR DisProt; DP03022; -.
DR Gene3D; 2.160.20.10; -; 1.
DR InterPro; IPR033806; CDI_toxin_Bp1026b-like.
DR InterPro; IPR040559; CdiA_C.
DR InterPro; IPR024973; ESPR.
DR InterPro; IPR008619; Filamentous_hemagglutn_rpt.
DR InterPro; IPR008638; Filamn_hemagglutn_N.
DR InterPro; IPR025157; Hemagglutinin_rpt.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR Pfam; PF18451; CdiA_C; 1.
DR Pfam; PF13018; ESPR; 1.
DR Pfam; PF05594; Fil_haemagg; 5.
DR Pfam; PF13332; Fil_haemagg_2; 3.
DR Pfam; PF05860; Haemagg_act; 1.
DR SMART; SM00912; Haemagg_act; 1.
DR SUPFAM; SSF51126; SSF51126; 1.
DR TIGRFAMs; TIGR01901; adhes_NPXG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Membrane; Nuclease; RNA-binding;
KW Secreted; Target cell cytoplasm; Toxin; Transmembrane; Transmembrane helix;
KW tRNA-binding; Virulence.
FT CHAIN 1..3122
FT /note="tRNA nuclease CdiA-2"
FT /id="PRO_0000429691"
FT TRANSMEM 54..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 36..205
FT /note="Two-partner system transport domain (TPS)"
FT /evidence="ECO:0000305"
FT REGION 256..1254
FT /note="FHA-1"
FT /evidence="ECO:0000305"
FT REGION 492..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1345..1635
FT /note="Receptor binding domain (RBD)"
FT /evidence="ECO:0000250|UniProtKB:A0A1S4NYE3"
FT REGION 1790..1845
FT /note="Periplasmic FHA-1 repeat (pFR)"
FT /evidence="ECO:0000305"
FT REGION 1947..2085
FT /note="FHA-2"
FT /evidence="ECO:0000305"
FT REGION 2002..2031
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2086..2825
FT /note="Pretoxin (PT) domain"
FT /evidence="ECO:0000305"
FT REGION 2151..2174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2325..2352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2821..3122
FT /note="C-terminal effector domain (CT), has tRNA nuclease
FT activity"
FT /evidence="ECO:0000269|PubMed:22435733"
FT REGION 2948..3122
FT /note="Truncated CT domain, has tRNA nuclease activity,
FT sufficient for interaction with CdiI-2"
FT REGION 2948..3000
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2987..3122
FT /note="Has tRNase activity"
FT /evidence="ECO:0000269|PubMed:26305955"
FT MOTIF 2826..2829
FT /note="ELYN C-terminal motif"
FT /evidence="ECO:0000305|PubMed:22435733"
FT COMPBIAS 2326..2352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 3012
FT /evidence="ECO:0000305|PubMed:23236156,
FT ECO:0000305|PubMed:27445337"
FT ACT_SITE 3039
FT /evidence="ECO:0000305|PubMed:23236156,
FT ECO:0000305|PubMed:27445337"
FT ACT_SITE 3048
FT /evidence="ECO:0000305|PubMed:23236156,
FT ECO:0000305|PubMed:27445337"
FT ACT_SITE 3067
FT /evidence="ECO:0000305|PubMed:23236156,
FT ECO:0000305|PubMed:27445337"
FT MUTAGEN 3039
FT /note="D->A: CT fragment not toxic in E.coli, no longer has
FT tRNA nuclease activity. Truncated CT fragment no longer has
FT nuclease activity. Unable to inhibit target cell growth
FT when expressed as whole cdiAIB locus in B.thailandensis. CT
FT fragment still binds tRNA."
FT /evidence="ECO:0000269|PubMed:22435733,
FT ECO:0000269|PubMed:27445337"
SQ SEQUENCE 3122 AA; 310224 MW; 2B2EC06CFD835534 CRC64;
MNKNRYRVVF NRARGALMVV QENGRASHGS GSRDARAGVV PAWLSLSPFA LRHVALAVLV
AAGVVPIWVN AQVVAGGAHA PSVIQTQNGL QQVNINRPGA SGVSMNTYNQ FDVPKPGIIL
NNSPINVQTQ LGGIIGGNPN FQAGDAARLI VNQVNSNNPS FIRGKVEIGG AAAQLVIANQ
AGLVVDGGGF LNTSRATLTT GNPNFGPDGS LTGFNVNQGL ISVVGAGLDT ANVDQVDLLA
RAVQINAKAY AKTLNVVAGS NQVDYNTLNA TPIAANGPAP TIAIDVSQLG GMYANRVFLV
SSENGVGVAN AGDIAAQAGD LTLQANGRLV LSGHTNAAGN MSLSASGGIQ NSGVTYGKQS
VTITTGADLT NSGALTAQQN LTANVGSLNS TGTLGAGINV DSTVGTSGDL NVTSSGQLTA
TGTNSAAGNA TFTGSGVNLS NSATAANGNL ALTATAGDVN LAGSTVSAKG AVNAQASGTV
VNDRGNLSSG AGMTLGGGSL SNQGGRANSQ GPLSVQMAGT VSNQNGMLSS QSTADVRGSA
IQNNAGLIQS AGKQTIAGAS IDNSAGRLIS LNADGLSVTA TGALTNAAGA NVSGDPGGVI
GGKGDVTVQG NTVTNSGSMS ADATLHVIGQ SVDNGNGALH AGQTTTVDAG NHLSNAGGRV
EGQSAVLNGA TLDNSQGTVN AATVSLNGTT LLNHGGTVTQ TGTGPMTVAI TDTLDNSNNG
LIQTRSTDLS LTSTTLINDN GGTITHVGPG TLTVGNGSGT VSNKAGAIAS NGRTVLQGKT
IDNSAGSASG QTGLSVNAAD SITNLGGKLT SNANVDVTAG GALVNDGGEL GSKTAATTIH
SASLSNLNGK IVSPTLTATV AGLLDNSQNG DFEANQLALT AANLKNQGGH ISQWQSGPTT
LAVSGTLDNS NGGVIQTNST DLTLAPAVLD NSKGTITHGG TGTLTLTPGN GAGALQNTGG
TIGTNGQAIV KAGSLDNGSG VIAAKLGLSA TIAGAMNNTQ GLMRSNAALS IISNGALSNH
QGHIEAGTPG DTSTLSIQAA SIDNTDGAVH DFGTGKMTVQ GGSQIVNSHA GGVDGMGQMT
GQGDVTIGAA SISNTQGGQL MGANLLIQGA TLDNSGGQVG NVANATGDVN VAMSGAVTNT
NGSITSTRDL SVAASTLLGG GAYSAARDAA INLQGDFTTT PQTQFNIGRD LTFTLPGTFA
NSANLQSVHN LTVNAGNIVN TGAMTAGSLL STHSGDLTNY GAMVGGSVAI QASGTVSNLG
PVALIGASDT SGLLEIVAHD IENRDDTTLG DSMPTTTIFG LGKVALAGGK DANGNYTNAA
LINNSSAAIQ SGASMELHAD KVTNTRRVMQ TSGNTSQVDP ALLQQLGISM SGCAAYYIAA
CSGQDVHWIN LFHDPNYPDY DPAPIIAALK LQPGGVFTVP PNGGQWNSGY QYTTYEGKAT
ANTVTKLSPG AQIASGGDLD ASTVKTFQNY WSSVTAAGNI KQPASLDMDG WGATGQQAPG
VTVVYSGYYH YNNYDNSEHN WTLPFGDKPF VGGPGGYTQA APADVRQYSL PDYRSTWGAN
GTISGNGVSV NNTAANATIP SLGLLPGQAV PGLTIGTVSG NASGTQSGAA AIKGGTPTWV
DPVIASATAV NVLSNLTIPQ GGLYRPNSAP NPTYLIETNP AFTRMNNFLS SDYYLNQIGV
NPLTTEKRLG DGFYEQQLVR NQVTQLTGKA VLGPYTDLQG MYQSLMLAGA EWSKSLNLPL
GMSLSAQQVA ALTTNVIIMQ TETVGGQQVL VPVVYLAKAD QQNANGPLIT AGNIDLKNTQ
VFTNSGTVKA DTTLALQGKQ IDNAFGALQS GGLTSLDTTG NVDLTSANVK AGSLDLNAGN
KLILDTATQT THQVSRDGAT SDKTTLGPAA NLNVAGDASI KTGGDFQQNA GNLNVGGNLN
ANIGGNWNLG VQQTGEHKVV QRANGVSDTD LNSATGSTVN VGGKSAIGVG GDLTAQGARL
DFGQGGTVAA KGNVTFGAAS TTSTINANSS GDQGNRSYAE TRHGSDQALT GTTVKGGDTL
NVVSGKDINV IGSTIDLKKG DANLLAAGDV NVGAVTERHV YNSRETHSRS GVVSGTKIAS
SQDATSTVAN GSLISADGVS IGSGKDINVQ GSTVVGTHDV ALNAAHDVNI TTSQDTSQSS
TTYQEQHSGL MSGGGLSFSV GNSKLAQQNQ SSSVTNNAST VGSVDGNLTV NAGNTLHVKG
SDLVAGKDVT GTAANIVVDS ATDTTRQAQQ QQTSKSGLTV GLSGSVGDAI NNAISETQAA
RESAKDSNGR ASALHSIAAA GDVAFGGLGA KALLDGAKGP QAPSIGVQVS VGSSHSSMQS
SEDQTIQRGS SINAGGNAKL IATGNGTPKD GNITIAGSNV NAANVALIAN NQVNLVNTTD
TDKTQSSNSS SGSSVGVSIG TNGIGVSASM QRAHGDGNSD AAIQNNTHIN ASQTATIVSG
GDTNVIGANV NANKVVADVG GNLNVASVQD TTVSAAHQSS AGGGFTISQT GGGASFSAQN
GHADGNYAGV NEQAGIQAGS GGFDVTVKGN TDLKGAYIAS TADASKNSLT TGTLTTSDIE
NHSHYSANSA GFSAGASVGV STKAVGPSSV SGSGGVTPMV FQNDSGDQSA TTKSAVSAGA
INITKPGEQT QDVANLNRDA TNLNGTVSKT PDVQKMLSQQ ADTMNAAQAA GQTVSQGIGL
YADGKRKDAI DAAKAAYERG DLVAMQSYID QAKSWDEGGA SRAGLQATGG ALIGGLGGGS
VLTAIGGAAG AGTSSLLAGQ AEKISKSVGD MTGSSLVGNI AANVAATVGG ALVGGSAGAA
MASNVELYNA GNDPQKTDDR ATIAGLQGLL NQAVAAGAKG LSTIANARNA IGNAISGALD
SAADQFGTLM KRDAEGKMSQ SPAELVSQGV ANGINTVLGS KGGEPPLAGP SAVAVDSLTG
QAANAALGAT DRTPPSNAIL SNSNSDNNST QGSQSGTVTK TPNPEATGSL SGKPTQIPPL
SDEVTTRSLI RENQSAVTLA NKGYDVVQNP EVLGPKNPDY TINGQVFDNY APATGNVRNI
ATTISNKVSS GQASNIVVNL ADSSASPAAI EAQINSYPIP GLGKVIVIDK LGNITIIKPK
GN
