CDIA_ECOLX
ID CDIA_ECOLX Reviewed; 3132 AA.
AC Q3YL96;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Toxin CdiA {ECO:0000303|PubMed:16109881};
DE AltName: Full=CdiA-EC93;
DE Flags: Precursor;
GN Name=cdiA {ECO:0000303|PubMed:16109881};
OS Escherichia coli.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CLEAVAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=EC93;
RX PubMed=16109881; DOI=10.1126/science.1115109;
RA Aoki S.K., Pamma R., Hernday A.D., Bickham J.E., Braaten B.A., Low D.A.;
RT "Contact-dependent inhibition of growth in Escherichia coli.";
RL Science 309:1245-1248(2005).
RN [2]
RP FUNCTION.
RC STRAIN=EC93;
RX PubMed=19124575; DOI=10.1128/jb.01437-08;
RA Aoki S.K., Webb J.S., Braaten B.A., Low D.A.;
RT "Contact-dependent growth inhibition causes reversible metabolic
RT downregulation in Escherichia coli.";
RL J. Bacteriol. 191:1777-1786(2009).
RN [3]
RP FUNCTION, STRAIN SPECIFICITY, DOMAIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=EC93;
RX PubMed=21085179; DOI=10.1038/nature09490;
RA Aoki S.K., Diner E.J., de Roodenbeke C.T., Burgess B.R., Poole S.J.,
RA Braaten B.A., Jones A.M., Webb J.S., Hayes C.S., Cotter P.A., Low D.A.;
RT "A widespread family of polymorphic contact-dependent toxin delivery
RT systems in bacteria.";
RL Nature 468:439-442(2010).
RN [4]
RP FUNCTION, AND STRAIN SPECIFICITY.
RC STRAIN=EC93;
RX PubMed=23882017; DOI=10.1128/mbio.00480-13;
RA Ruhe Z.C., Wallace A.B., Low D.A., Hayes C.S.;
RT "Receptor polymorphism restricts contact-dependent growth inhibition to
RT members of the same species.";
RL MBio 4:E00480-E00480(2013).
RN [5]
RP FUNCTION, REQUIRES PMF FOR TRANSLOCATION, AND SUBCELLULAR LOCATION.
RC STRAIN=EC93;
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 [6]
RP FUNCTION IN BIOFILM FORMATION, DOMAIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=EC93;
RX DOI=10.1111/mmi.13114;
RA Ruhe Z.C., Townsley L., Wallace A.B., King A., Van der Woude M.W.,
RA Low D.A., Yildiz F.H., Hayes C.S.;
RT "CdiA promotes receptor-independent intercellular adhesion.";
RL Mol. Microbiol. 98:175-192(2015).
RN [7]
RP DOMAIN.
RC STRAIN=EC93;
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 [8]
RP SUBCELLULAR LOCATION, DOMAIN, AND TOPOLOGY.
RC STRAIN=EC93;
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).
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 (target cell counts
CC decrease 1000- to 10(5)-fold) in a contact-dependent fashion.
CC Inhibitory cells must be in logarithmic (not stationary) phase to
CC inhibit growth of their targets, but protein synthesis is not necessary
CC (PubMed:16109881, PubMed:25174572). The presence of P or S but not type
CC 1 pili protects the target cells against growth inhibition for this
CC CDI. BamA on the outer membrane of target cells acts as a receptor for
CC CdiA, while target cell multidrug efflux pump AcrB facilitates its
CC transport into the cytoplasm (PubMed:16109881). Outer membrane receptor
CC function is dependent on extracellular loops of BamA (PubMed:23882017).
CC Cells undergoing CDI show a 2- to 5-fold reversible decrease in aerobic
CC respiration, proton motive force and steady-state ATP levels,
CC suggesting this CT module is an ionophore that disrupts the target
CC cell's inner cell membrane. Growth recovery requires an energy source.
CC Cells expressing this protein in the absence of CdiI initially form
CC filaments, some of which contain multiple nucleoids, while others are
CC devoid of nucleoids. CDI cells induce the phage shock response, but
CC pspA is not required for recovery from CDI (PubMed:19124575). CDI is
CC neutralized by its cognate immunity protein CdiI, but not by non-
CC cognate CdiI from other bacteria with different CDI systems
CC (PubMed:21085179). Plays a role in biofilm formation, a region N-
CC terminal to residue 644 is implicated in this receptor-independent cell
CC adhesion (Ref.6). {ECO:0000269|PubMed:16109881,
CC ECO:0000269|PubMed:19124575, ECO:0000269|PubMed:21085179,
CC ECO:0000269|PubMed:23882017, ECO:0000269|PubMed:25174572,
CC ECO:0000269|Ref.6}.
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 (BamA 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 (multidrug efflux pump AcrB for this CDI).
CC {ECO:0000305|PubMed:30388452}.
CC -!- SUBUNIT: Probably interacts with cognate immunity protein CdiI.
CC {ECO:0000305|PubMed:23882017}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000303|PubMed:28351921}. 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). Toxin translocation into the target
CC cell depends on the proton motive force of the target cell, but not on
CC tolA or tonB (PubMed:25174572). Forms multiple filaments that extend
CC away from the host cell surface, averaging 33 nm long; protein
CC truncated at residue 1929 still forms filaments (PubMed:30388452).
CC {ECO:0000269|PubMed:25174572, ECO:0000269|PubMed:30388452,
CC ECO:0000305}.
CC -!- DOMAIN: The CDI activity resides in the approximately 230 residue C-
CC terminal (CT) domain; exchanging the C-terminal (CT) domain and cdiI
CC gene between different strains confers resistance within cognate but
CC not non-cognate systems (i.e. CdiI-EC93 neutralizes CdiA-CT from strain
CC EC93 but not CdiA-CT from E.coli strain 536 / UPEC, Y.pestis strain
CC CO92 or D.dadantii strain 3937). Intracellular expression of the last
CC 223 residues of CdiA-EC93 inhibits growth, which can be relieved by
CC CdiI from strain EC93 but not 536 / UPEC (PubMed:21085179). Exchanging
CC the outer membrane receptor-binding domains between proteins exchanges
CC the receptors recognized by CdiA (PubMed:28351921). Extracellular
CC filaments are formed by the N-terminus of the protein (residues 1-1929)
CC (PubMed:30388452). {ECO:0000269|PubMed:21085179,
CC ECO:0000269|PubMed:28351921, ECO:0000269|PubMed:30388452}.
CC -!- PTM: Expressed as 303 kDa protein which can be processed to 284 kDa and
CC 195 kDa forms. {ECO:0000269|PubMed:16109881}.
CC -!- DISRUPTION PHENOTYPE: Loss of contact-dependent growth inhibition
CC (PubMed:16109881). In competition experiments between EC93 cells
CC encoding or deleted for cdiA and cdiI, cdiA/cdiI minus cells were
CC quickly outcompeted by wild-type, probably due to intraspecies CDI
CC (PubMed:21085179). Decreased biofilm formation (Ref.6).
CC {ECO:0000269|PubMed:16109881, ECO:0000269|PubMed:21085179,
CC ECO:0000269|Ref.6}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CdiA toxin
CC family. {ECO:0000305}.
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DR EMBL; DQ100454; AAZ57198.1; -; Genomic_DNA.
DR SMR; Q3YL96; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0003824; F:catalytic activity; IEA:UniProt.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0043170; P:macromolecule metabolic process; IEA:UniProt.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IEA:UniProt.
DR GO; GO:0044238; P:primary metabolic process; IEA:UniProt.
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; 5.
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; 16.
PE 1: Evidence at protein level;
KW Cell adhesion; Secreted; Signal; Target cell cytoplasm; Toxin; Virulence.
FT SIGNAL 1..32
FT /note="Signal"
FT /evidence="ECO:0000303|PubMed:28351921"
FT CHAIN 33..3132
FT /note="Toxin CdiA"
FT /id="PRO_0000432089"
FT REGION 36..322
FT /note="Two-partner system transport domain (TPS)"
FT /evidence="ECO:0000305|Ref.6"
FT REGION 351..1378
FT /note="FHA-1"
FT /evidence="ECO:0000305|PubMed:30388452"
FT REGION 1379..1635
FT /note="Receptor-binding domain (RBD)"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 1636..1820
FT /note="YP domain"
FT /evidence="ECO:0000305|PubMed:30388452"
FT REGION 1821..1859
FT /note="Periplasmic FHA-1 repeat (pFR)"
FT /evidence="ECO:0000305|PubMed:30388452"
FT REGION 1930..2526
FT /note="FHA-2"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 2195..2228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2456..2497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2862..2904
FT /note="Pre-toxin (PT) domain"
FT /evidence="ECO:0000305|PubMed:28351921"
FT REGION 2909..3121
FT /note="C-terminal effector domain (CT)"
FT /evidence="ECO:0000305|PubMed:21085179"
FT MOTIF 2905..2908
FT /note="VENN CT cleavage motif"
FT /evidence="ECO:0000305"
FT COMPBIAS 2464..2497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 3132 AA; 318904 MW; 3C5F96FFA0116D86 CRC64;
MHQPPVRFTY RLLSYLVSAI IAGQPLLPAV GAVITPQNGA GMDKAANGVP VVNIATPNGA
GISHNRFTDY NVGKEGLILN NATGKLNPTQ LGGLIQNNPN LKAGGEAKGI INEVTGGKRS
LLQGYTEVAG KAANVMVANP YGITCDGCGF INTPHATLTT GKPVMNADGS LQALEVTEGS
ITINGAGLDG TRSDAVSIIA RATEVNAALH AKDLTVTAGA NRITADGRVS ALKGEGNVPK
VAVDTGALGG MYARRIHLTS TESGVGVNLG NLYAREGDII LSSSGKLVLK NSLAGGNTTV
TGTDVSLSGD NKAGGNLSVT GTTGLTLNQS RLVTDKNLVL SSSGQIVQNG GELTAGQNAM
LSAQHLNQTS GTVNAAENVT LTTTDDTTLK GRSVAGKTLT VSSGSLNNGG TLVAGRDATV
KTGTFSNTGT VQGNGLKVTA TDLTSTGSIK SGSTLDISAR NATLSGDAGA KDRALVTVSG
TLENRGRLVS DDVLTLSATQ INNSGTLSGA KELVASADTL TTTEKSVTNS DGNLMLDSAS
STLAGETSAG GTVSVKGNSL KTTTTAQTQG NSVSVDVQNA QLDGTQAARD ILTLNASEKL
THSGKSSAPS LSLSAPELTS SGVLVGSALN TQSQTLTNSG LLQGKASLTV NTQRLDNQQN
GTLYSAADLT LDIPDIRNSG LITGDNGLML NAVSLSNPGK IIADTLSVRA TTLDGDGLLQ
GAGALALAGD TLSLGSNGRW LTAGDLSLRG KTLHTAGTTQ GQNLTVQADR WANSGSVQAT
GNLTASATGQ LTSTGDIMSQ GDTTLNAATT DNRGSLLSAG TLSLDGNSLD NSGTVQGNHV
TIRQNGVTNS GTLTGIAALT LAARMDMASP QPALMNNGGS LLTSGDLTIT AGSLANSGAI
QAADSLTARL TGELVSTAGS KVTSNGEMAL SALNLSNSGQ WIAKNLTLKA NSLTSAGDIT
GVDALTLTVN QTLNNHASGK LLSAGVLTLK ADSVKNDGQL QGNATTITAG QLTNGGHLQG
ETLTLAASGG VNNRSGGVLM SRNALNVSTA TLSNQGTIQG GGGVSLNATD RLQNDGKILS
GSNLTLTAQV LANTGSGLVQ AATLLLDVVN TVNGGRVLAT GSADVKGTTL NNTGTFQGAD
LLVNYHTFSN SGTLLGTSGL GVKGSSLLQN GTGRLYSAGN LLLDAQDFSG QGQVVATGDV
TLKLIAALTN HGTLAAGKTL SVTSQNAVTN GGVMQGDAMV LGAGEAFTNN GTLTAGKGNS
VFSAQRLFLN APGSLQAGGD VSLNSRSDIT ISGFTGTAGS LTMNVAGTLL NSALIYAGNN
LKLFTDRLHN QHGDILAGNS LWVQKDSSGT ANSEIINRSG NIETTRGDIT MNTAHLLNSW
DAISASHEVI PGSSHGVISP VPENNRWWGV VRHDGVEYLA VYWGKGATVP DEYRIRTGDT
ETVTVSASGH AARISGGADM HIRAGRLDNE ASFILAGGGM TLSGDTLNNQ GWQEGTTGKE
TVWRLASGSL PKAWFTEPWY KVYRQVSPDA TEASGTSPAG QYRAVISAAG DVSASFATDT
GNTTVMPRAG GAGNTITVPS LNSLTPPTVS QGVSGEALLN ESGTGITGPV WNDALPDTLK
DIPGALSLSG ASVSSYPLPS GNNGYFVPST DPDSPYLITV NPKLDGLGKV DSSLFAGLYD
LLRMQPGEAP RETDPAYTDE KQFLGSSYIL DRLGLKPEKD YRFLGDAAFD TRYVSNVILN
QTGSRYINGT GSDLAQMKYL MDSAAAQQKA LGLTFGVSLT AGQVAQLTRS LLWWESVTIN
GQTVMVPKLY LSPEDITLHN GSVISGNNVQ LAGGNITNSG SSINAQNDLL LDRTGSIDNL
NAGLINAGGA LNLKAIGDIG NISSVISGKT VSLESATGNI SNLTRTEQWA MNNGYNHFSG
TDTGPLAAVR ATDSLFMGAA GDISITGAAV SAGDSVLLAA GNDLNMNAIQ AGERRRYGGS
GWYETHAVAP TVTAGNSLML SAGRDVNSQA AGITAENSMD IRAGRDVNMA AESTGAGDHD
STFSMKTVHD SVRQQGTDMT SGGDITVTAG RDITSVATAV TAKGDIRVNA GHDIVLGTAT
ESDYHYSESG ETRNRLLSHQ TTRTITEDSV TREKGSLLSG NRVTVNAGNN LTVQGSDVVA
DRDVSLAADN HVDVLAATST DTSWRFKETK TSGLTGTGGI GFTTGSSKTT HDRREAGTTQ
SQSASTIGST AGNVSITAGK QAHISGSDVI ANRDISITGD SVVVDPGHDR RTVDEKFEQK
KSGLTVALSG AVGSAINNAV TMAREAKETS DSRLAALKGT QAVLSGVQAG VNHGLQQQSA
DPNNGIGVSI SLNHQQSKSE TKYQHDIVSG STLSAGNNVS VTATGKNKDH NNSGDMLITG
SQIKSGNDTS LNAQNDILLA AAADTRQTTG KNSSKGGGVG VSFGGGTNGG GLSIFAGING
SEGREKGNGT TWTETTLDAG KNVSLTSGRD TTLSGAQVSG EKVTADVGNN LTISSLQDSD
RYDSRQNRVA AGGSFTFGSM SGSGYASISQ DKIKSNYDSV REQSGIYAGK DGFDVTVGNH
TQLNGAVIAS TATDDKNSLN TNTLGWSDIH NQADYKASHT GISLSGGSGM SASQMVASNA
IAGAANALTG MSGSSGHAEG TTSSAISGGN LIIRNKESQK QDIAGLSRDP ENANGSIAPI
FDREKEQKRL QEAQVISQIS GQMSNIVMTY GETEAMKAAR KEHPGMSDAQ LRETPEYREV
MKGYGTGSTP QMVVQAITGV LGGLNAGNPG QVLAGGLNPA VAQLIKQATG DNREANLMAH
AVWGALAAQL GGNNAASGAA GAFSGELAAR YIIDNYYGGR TDNLSEQERQ QISMLATIAS
GIAGGLVGNS TSAAGTGAQA GRNSVENNAM SGLEGFGTGF QSYVQAQEAL VNNTNLTDKN
GKVLNPATPE EIKYASDKLV TGSIPEGQDP ARGLLISWGA GASVFGGELI APAVGTVAVI
GGTLLGGTTD AVKQFLTLKP GEQYSTTDTL IAAGEGGLTQ GKGVIFSTFI NTMGAYLGSK
AKGEDPTGPM VGNAIGTALG NKAGDKFTKE MLSRGFGSVT SEVTGTVTGS VIGTVTDYQI
EKLGKGNKEG AK
