CDIA_ECOST
ID CDIA_ECOST Reviewed; 3253 AA.
AC A0A1S4NYE3;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 2.
DT 25-MAY-2022, entry version 17.
DE RecName: Full=tRNA nuclease CdiA {ECO:0000303|PubMed:29923643};
DE Short=tRNase CdiA {ECO:0000303|PubMed:29923643};
DE EC=3.1.-.- {ECO:0000269|PubMed:29923643};
DE AltName: Full=Contact-dependent inhibitor A {ECO:0000303|PubMed:28351921};
DE Short=CdiA-STECO31 {ECO:0000303|PubMed:29923643};
DE AltName: Full=Toxin CdiA;
DE Flags: Precursor;
GN Name=cdiA {ECO:0000303|PubMed:28351921}; Synonyms=ECSTECO31_4009;
OS Escherichia coli (strain STEC_O31).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=754081;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=STEC_O31;
RA Rasko D., Redman J., Daugherty S.C., Tallon L., Sadzewicz L., Jones K.,
RA Santana-Cruz I., Liu X.;
RL Submitted (JUL-2012) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, IDENTIFICATION OF RECEPTORS, AND DOMAIN.
RC STRAIN=EPI100, and STEC_O31;
RX PubMed=28351921; DOI=10.1128/mbio.00290-17;
RA Ruhe Z.C., Nguyen J.Y., Xiong J., Koskiniemi S., Beck C.M., Perkins B.R.,
RA Low D.A., Hayes C.S.;
RT "CdiA effectors use modular receptor-binding domains to recognize target
RT bacteria.";
RL MBio 8:0-0(2017).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, TOPOLOGY, AND MUTAGENESIS OF
RP ASN-2934.
RC STRAIN=STEC_O31;
RX PubMed=30388452; DOI=10.1016/j.cell.2018.10.033;
RA Ruhe Z.C., Subramanian P., Song K., Nguyen J.Y., Stevens T.A., Low D.A.,
RA Jensen G.J., Hayes C.S.;
RT "Programmed secretion arrest and receptor-triggered toxin export during
RT antibacterial contact-dependent growth inhibition.";
RL Cell 175:921-933(2018).
RN [4] {ECO:0000312|PDB:5HKQ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 3111-3253 IN COMPLEX WITH CDII,
RP FUNCTION, LACK OF COFACTOR, SUBUNIT, DOMAIN, AND MUTAGENESIS OF HIS-3117;
RP HIS-3134; LYS-3191; THR-3192; ASN-3249 AND HIS-3251.
RC STRAIN=STEC_O31;
RX PubMed=29923643; DOI=10.1111/mmi.14007;
RA Michalska K., Quan Nhan D., Willett J.L.E., Stols L.M., Eschenfeldt W.H.,
RA Jones A.M., Nguyen J.Y., Koskiniemi S., Low D.A., Goulding C.W.,
RA Joachimiak A., Hayes C.S.;
RT "Functional plasticity of antibacterial EndoU toxins.";
RL Mol. Microbiol. 109:509-527(2018).
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 target bacteria in a contact-
CC dependent fashion (target cell counts decrease 1000- to 10000-fold with
CC this CDI) (PubMed:28351921, PubMed:29923643). Uses outer membrane
CC nucleoside transporter Tsx on target cells as a receptor
CC (PubMed:28351921). Gains access to the cytoplasm of target cells by
CC using integral inner membrane protein PTS system glucose-specific EIICB
CC component (ptsG) (Probable). Targeting of the C-terminal domain (CT)
CC domain (residues 2931-3253) in the absence of immunity protein inhibits
CC cell growth and causes tRNA(UUC-Glu) cleavage; expression of cognate
CC immunity protein CdiI-STECO31 neutralizes growth inhibition leaving
CC tRNA(UUC-Glu) is intact, whereas non-cognate immunity proteins do not
CC confer protection (PubMed:29923643). The CT domain cleaves tRNA; it is
CC most active against tRNA(UUC-Glu), but also has modest activity against
CC tRNA(GUC-Asp), tRNA(UUG-Gln), tRNA(CCC-Gly), tRNA(UCC-Gly), tRNA(GCC-
CC Gly), tRNA(UUU-Lys), tRNA(GGU-Thr) and tRNA(CCA-Trp); tRNA cleavage is
CC inhibited by cognate immunity protein CdiI. Cleavage of tRNA(UUC-Glu)
CC occurs in the anticodon loop between cytosine(37) and 2-
CC methyladenosine(38) (C37-m2A38) and probably also occurs in the
CC anticodon loop of other tRNAs as well (PubMed:29923643).
CC {ECO:0000269|PubMed:28351921, ECO:0000269|PubMed:29923643,
CC ECO:0000305|PubMed:28351921}.
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 (33 nm long) with the
CC receptor-binding domain (RBD) at its extremity; in the secretion
CC arrested state the C-terminus of the RBD and YP domains form a hairpin-
CC like structure as the FHA-2, PT and CT domains are periplasmic. The YP
CC domain is probably responsible for this arrest at the point where it
CC re-enters the host cell periplasm. Upon binding to a target cell outer
CC membrane receptor (Tsx for this CDI) a signal is transmitted to
CC activate secretion. The filament becomes about 5 nm longer, the rest of
CC CdiA is secreted and the FHA-2 domain becomes stably associated with
CC the target cell's outer membrane where it facilitates entry of the
CC toxic CT domain into the target cell periplasm. From there the toxic CT
CC domain is cleaved and gains access to the target cell cytoplasm via an
CC inner membrane protein (PTS system glucose-specific EIICB component,
CC ptsG for this CDI). {ECO:0000305|PubMed:30388452}.
CC -!- COFACTOR:
CC Note=tRNase activity is metal-independent.
CC {ECO:0000269|PubMed:29923643};
CC -!- SUBUNIT: Forms a 1:1 complex with cognate immunity protein CdiI-
CC STECO31. {ECO:0000269|PubMed:29923643}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000255}. Target cell, target cell
CC cytoplasm {ECO:0000305|PubMed:30388452}. Note=Secreted to the cell
CC surface by CdiB, its two partner secretion pathway (TPS) partner
CC (Probable). Toxin translocation into the target cell depends on the
CC proton motive force of the target cell, but not on tolA or tonB (By
CC similarity). Forms filaments that extend about 33 nm away from the host
CC cell surface; multiple filaments can be found on a single cell
CC (PubMed:30388452). {ECO:0000250|UniProtKB:Q3YL96,
CC ECO:0000269|PubMed:30388452}.
CC -!- DOMAIN: The FHA1 domain comprises the bulk of the extended filament,
CC deletion of 100 internal residues (900-999) has a very small defect in
CC CDI and target cell adhesion. The receptor binding domain (RBD)
CC recognizes Tsx on target cells. The YP domain is required for stable
CC presentation to the target cellmfac in liquid but not on solid growth
CC media. The pFR and FHA-2 domains are critical for delivery of the CT to
CC the target cell periplasm; deletions within these regions (1854-1954
CC and 2324-2423 respectively) lead to aberrant processing by target cell
CC OmpT. FHA-2 is required for stable association with the target cell
CC outer membrane. The PT domain is also required for CT delivery into
CC target bacteria; it is transferred into the target cell and may be
CC involved in autoproteolysis to release the CT domain (PubMed:30388452).
CC The C-terminal effector domain (CT) has toxic, tRNase activity and
CC binds to cognate immunity protein CdiI-STECO31 (PubMed:29923643).
CC {ECO:0000269|PubMed:29923643, ECO:0000269|PubMed:30388452}.
CC -!- PTM: The CT domain is cleaved upon binding to receptor Tsx on target
CC cells. {ECO:0000269|PubMed:30388452}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CdiA toxin
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the bacterial EndoU
CC family. {ECO:0000305}.
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DR EMBL; AFEX01000038; EJK94116.1; -; Genomic_DNA.
DR RefSeq; WP_001385946.1; NZ_AFEX01000038.1.
DR PDB; 5HKQ; X-ray; 2.00 A; A=3111-3253.
DR PDBsum; 5HKQ; -.
DR SMR; A0A1S4NYE3; -.
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; IPR008638; Filamn_hemagglutn_N.
DR InterPro; IPR025157; Hemagglutinin_rpt.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR006914; VENN_dom.
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 SUPFAM; SSF51126; SSF51126; 1.
DR TIGRFAMs; TIGR01901; adhes_NPXG; 1.
DR TIGRFAMs; TIGR01731; fil_hemag_20aa; 19.
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:0000303|PubMed:28351921"
FT CHAIN 33..3253
FT /note="tRNA nuclease CdiA"
FT /id="PRO_0000446869"
FT REGION 36..322
FT /note="Two-partner system transport domain (TPS)"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 351..1384
FT /note="FHA-1"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 1385..1656
FT /note="Receptor binding domain (RBD)"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 1657..1841
FT /note="YP domain"
FT /evidence="ECO:0000305|PubMed:30388452"
FT REGION 1842..1902
FT /note="Periplasmic FHA-1 repeat (pFR)"
FT /evidence="ECO:0000305|PubMed:28351921,
FT ECO:0000305|PubMed:30388452"
FT REGION 1944..2548
FT /note="FHA-2"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 2228..2252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2362..2410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2483..2503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2687..2712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2888..2930
FT /note="Pretoxin (PT) domain"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 2931..3253
FT /note="C-terminal effector domain (CT)"
FT /evidence="ECO:0000303|PubMed:29923643"
FT MOTIF 2931..2934
FT /note="VDNN CT cleavage motif"
FT /evidence="ECO:0000305|PubMed:30388452"
FT COMPBIAS 2364..2407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 2934
FT /note="N->A: Prevents cleavage of CT and thus CDI, no
FT effect on target cell adhesion."
FT /evidence="ECO:0000269|PubMed:30388452"
FT MUTAGEN 3117
FT /note="H->A: Loss of growth inhibition, no tRNA cleavage by
FT targeted CT domain, in vitro CT domain has very little
FT tRNase activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT MUTAGEN 3134
FT /note="H->A: Loss of growth inhibition, no tRNA cleavage by
FT targeted CT domain, in vitro CT domain has no tRNase
FT activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT MUTAGEN 3191
FT /note="K->A: Loss of growth inhibition, partial tRNA
FT cleavage by targeted CT domain, in vitro CT domain has very
FT little tRNase activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT MUTAGEN 3192
FT /note="T->A: Loss of growth inhibition, partial tRNA
FT cleavage by targeted CT domain, in vitro CT domain has
FT little tRNase activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT MUTAGEN 3249
FT /note="N->A: Retains growth inhibition and tRNA cleavage by
FT isolated CT domain, in vitro CT domain has nearly wild-type
FT tRNase activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT MUTAGEN 3251
FT /note="H->A: Loss of growth inhibition, partial tRNA
FT cleavage by targeted CT domain, in vitro CT domain has very
FT little tRNase activity."
FT /evidence="ECO:0000269|PubMed:29923643"
FT STRAND 3118..3125
FT /evidence="ECO:0007829|PDB:5HKQ"
FT TURN 3126..3128
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3129..3132
FT /evidence="ECO:0007829|PDB:5HKQ"
FT HELIX 3136..3145
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3149..3155
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3161..3171
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3177..3184
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3189..3194
FT /evidence="ECO:0007829|PDB:5HKQ"
FT TURN 3196..3198
FT /evidence="ECO:0007829|PDB:5HKQ"
FT HELIX 3201..3222
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3225..3231
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3234..3241
FT /evidence="ECO:0007829|PDB:5HKQ"
FT TURN 3242..3245
FT /evidence="ECO:0007829|PDB:5HKQ"
FT STRAND 3246..3252
FT /evidence="ECO:0007829|PDB:5HKQ"
SQ SEQUENCE 3253 AA; 332547 MW; 10036EEDE3DCBE06 CRC64;
MHQPPVRFPY RLLSYLISTI IAGQPLLPAV GAVITPQNGA GMDKAANGVP VVNIATPNGA
GISHNRFTDY NVGKEGLILN NATGKLNPTQ LGGLIQNNPN LKAGGEAKGI INEVTGGNRS
LLQGYTEVAG KAANVMVANP YGITCDGCGF INTPRATLTT GRPVMNADGS LQALEVTEGS
ITINGAGLDG TRSDAVSIIA RATEVNAALH AKDLTVTAGA NRVTADGRVS ALKGEGDVPK
VAVDTGALGG MYARRIHLTS TESGVGVNLG NLYAREGDII LSSSGKLVLK NSLAGGNTTV
TGTDVSLSGD NKAGGNLSVT GTTGLTLNQS RLVTDKNLVL SSSGQIVQNG GELTAGQNAM
LSAQHLNQTS GAVNAAENVT LTTTGGITLK GRSVAGKTLT VSSGSLNNGG TLGAGRDATV
KTGTFSNTGA VQGNGLKVTA TDLTSTGSIK SGSTLDISAR NATLSGDAGA KDSARVTVSG
TLENRGRLVS DDVLTLSATQ INNSGTLSGA KELVASADTL TTTEKSVTNS DGNLMLNSAS
STLAGETSAG GTVSVKGNSL KTTTTAQTQG NSVSVDVQNA QLDGTQAARD ILTLNASEKL
THSGKSSAPS LSLSAPELTS SGVLVASALN TQSQTLTNSG LLQGEASLTV NTQRLDNQQN
GTLYSAADLT LDIPDIRNSG LITGDNGLTL NTASLSNPGK ITADTLNVRA TTLDGDGLLQ
GAAALALAGD TLSQGSHGRW LTAGDLSLRG KTLNTAGTTQ GQNLTVQADR WANSGSVLAT
GNLTASATGQ LTSTGDIMSQ GDTTLNAATT DNRGSLLSAG TLSLDGNSLD NSGTVQGNHV
TLHHRSTDNS GTVTGLSGLT LHSADGLTNS GALLSQNSLV LSAGDVTNSG RIQGQNITLD
ASSLTSSGAV QSALDLALTL SGDVIAATGS KITALGDARL TGKVLGNQGL ISAKTLEVNG
DSLSNSGEIS GVNSLNVTLS GNLQQHGKML TGGALNVNAR DISNSGQLQG ADNRITASSL
ANSGRVQGES GLTLTLLNAL TNQTSGVLLS QNVSALSAPV LTNDGTIQGN GKTTLSAATQ
AHNSGKILSG GELTFTTPDY SGSGWLQATD LLLNVAKLAG NGTVMAANQA TLTGNSLTNR
GLFQAAQLNV NTQTITNSGT LLGNQGLTIK GNNLNNAGGK VFSGGDMLAE MVSLSGAGQL
VALGNLTLKL TRGLTAQGVI AANKQLSVSS QGDITNGATL QGNGITLNAA GRLTNNGQLT
AGNGTTALSG SGIAMNASGS LQAGGDVSLT SRGDITLDAF TGTTGSLMLT AAGAVINTAL
LYAGNNLSLF ASTIRNHHGD MLAGDSLVMQ KDVSGAANAE VINTSGNIET TRGDITIRTG
HLLNQREGIN ETKSYIPVEN VAVPDGANSV SVRVGDLGED GWGYYVKSWS GTAGGGFDAW
AVPTEKGATR KFLTGTTRVD VGATGGDARI SAGNNLLIDA DKLDNTGSHL LASGFVSLSG
SQLNNQSFFG YTQDEYNVYR YYGKLAMIPN DGHLQYGDAS ADDRVTFTLS GAPEYVTRDT
GQALRAVIQA GKNVTAVFSS DISNTSTTSN AGRITNTLAA PEINTPAEKN ISPRMAQLAP
DGTEMLTVTA PDWTDTITRL TIGSGTDLAS GIVEGNYPLP SGNNGYFVPS ADPDSPYLIT
VNPKLDGLGK VDSSLFAGLY DLLRMHPGQA PRETDPAYTD EKQFPGSSYF LDRLGLKPEK
DYRFLGDAAF DTRYVSNYML NQIGGRYING VGSDTDQMRY LMDNAARAQK ALGLKFGVAL
TADQVAALDQ SILWYKAVTI KGQTVMVPEV YLSPKDVTLQ NGSIISGQNV HLAGGNVTNS
GSTLMAQNNL TIDSADSLGN LESGLINAGG ALGLKAMGDI NNISATITGK TVRLESLAGN
VNNLTRYSHW QLDAPEDSLA LKHTYTGSIA SVSAMDSLDI RADKNISVTG AEISAGDRAA
LIAGNDLSLN AIDRVSSRRH ANSESHQRSA GLTTITAGDS VMLSAGRDVS SQGAGIAAED
NITVRAGRDV NLLAEESVTG SSSYSKKKTV IDETVRQQGA EIASGGDTTI TAGRDITAVA
SSVTATGNIS VNAGRDVALT TATESDYHYL ETKKKSGGFL SKKTTHTISE NSATREAGAL
LSGNRVTVNA GDNLTVQGSD VVADRDVSLA AGNHVDVLAA TSTDTSWRFK ETKKSGLMGT
GGIGFTIGSS KTTHDRREAG TTQSQSASTI GSTAGNVSIT AGKQAHISGS DVIANRDISI
TGDSVVVDPG HDRRTVDEKF EQKKSGLTVA LSGTVGSAIN NAVTSAQETK ESSDSRLKAL
QATKTALSGV QAGQAAAMAT ATGDPNATGV SLSLTTQKSK SQQHSESDTV SGSTLNAGNN
LSVVATGKNR GDNRGDIVIA GSQLKAGGNT SLDAANDILL SGAANTQKTT GRNSSSGGGV
GVSIGAGKGA GISVFASVNA AKGSEKGNGT EWTETTTDSG KTVTINSGRD TVLNGAQVNG
NRIIADVGHD LLISSQQDTS KYDSKQTSVA AGGSFTFGSM TGSGYIAASR DKMKSRFDSV
AEQTGMFAGD GGFDITVGRH TQLDGAVIAS TATPDKNHLD TGTLGFSDLH NEADYKVSHS
GISLSGGGSF GDKFQGNMPG GMISAGGHSG HAEGTTQAAV AEGTITIRDR DNQKQNPADL
SRDPAHANDS ISPIFDKEKE QRRLQTVGLI SDIGSQVADI ARTQGELNAL KAAKEATGET
LPANATEKQR QEYLAKLRDT PEYKKEQEKY GTGSEIQLGI QAATAALQGL AGGNLAGALA
GASAPELAHL LKSTEKDPAV NAIAHAILGG AVAAMQGNNV AAGAAGAATG ELAARAIAGM
LYPGVKQSDL SEEQKQTIST LATVSAGLAG GLTGNSSASA AVGAQSGKNA VDNNYLSVSE
KTELEIAKQT LKNSKNPAER EKAQQKYDAL LEKDIASDKE VIAACGNGNA GSSACASARL
KVIASKEGYE DGPYNSKYSQ QYADAYGQIV NLLDITSVDV QNQQQVKDAM VSYFMATLGV
DQKTAQGYVE TTQGLEIAAA SMTPLFGQAV ANKITALVDK ANKYPSGIGF KINQPEHLAQ
LDGYSQKKGI SGAHNADVFN KAVVDNGVKI ISETPTGVRG ITQVQYEIPT KDAAGNTTGN
YKGNGAKPFE KTIYDPKIFT DEKMLQLGQE AAAIGYSNAI KNGLQAYDAK AGGVTFRVYI
DQKTGIVSNF HPK
