VGRG1_VIBCH
ID VGRG1_VIBCH Reviewed; 1163 AA.
AC Q9KS45;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Actin cross-linking toxin VgrG1;
DE EC=6.3.2.- {ECO:0000250|UniProtKB:A0A0H3AIG7};
GN Name=vgrG1 {ECO:0000303|PubMed:17873062};
GN Synonyms=vgrG-1 {ECO:0000303|PubMed:17873062};
GN OrderedLocusNames=VC_1416 {ECO:0000312|EMBL:AAF94573.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [2]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17873062; DOI=10.1073/pnas.0706532104;
RA Pukatzki S., Ma A.T., Revel A.T., Sturtevant D., Mekalanos J.J.;
RT "Type VI secretion system translocates a phage tail spike-like protein into
RT target cells where it cross-links actin.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:15508-15513(2007).
RN [3]
RP FUNCTION.
RX PubMed=20150509; DOI=10.1073/pnas.0915156107;
RA Ma A.T., Mekalanos J.J.;
RT "In vivo actin cross-linking induced by Vibrio cholerae type VI secretion
RT system is associated with intestinal inflammation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4365-4370(2010).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH PROTEIN VC1417.
RC STRAIN=V52;
RX PubMed=26150500; DOI=10.1073/pnas.1505317112;
RA Liang X., Moore R., Wilton M., Wong M.J., Lam L., Dong T.G.;
RT "Identification of divergent type VI secretion effectors using a conserved
RT chaperone domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:9106-9111(2015).
RN [5] {ECO:0007744|PDB:4GQK}
RP X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 717-1111 IN COMPLEX WITH ADP.
RA Nguyen V.S., Spinelli S., Derrez E., Durand E., Cambillau C.;
RT "Structure of Native VgrG1-ACD with ADP (no cations).";
RL Submitted (AUG-2012) to the PDB data bank.
CC -!- FUNCTION: Part of the type VI secretion system (T6SS) specialized
CC secretion system, which delivers several virulence factors in both
CC prokaryotic and eukaryotic cells during infection (PubMed:26150500).
CC Forms the spike at the tip of the elongating tube probably formed by
CC hemolysin co-regulated protein/Hcp. Allows the delivery of the TseL
CC antibacterial toxin to target cells where it exerts its toxicity
CC (PubMed:26150500). Acts also directly as an actin-directed toxin that
CC catalyzes the covalent cross-linking of host cytoplasmic monomeric
CC actin. Mediates the cross-link between 'Lys-50' of one monomer and
CC 'Glu-270' of another actin monomer, resulting in formation of highly
CC toxic actin oligomers that cause cell rounding (PubMed:17873062,
CC PubMed:20150509). The toxin can be highly efficient at very low
CC concentrations by acting on formin homology family proteins: toxic
CC actin oligomers bind with high affinity to formins and adversely affect
CC both nucleation and elongation abilities of formins, causing their
CC potent inhibition in both profilin-dependent and independent manners
CC (By similarity). Acts as an acid--amino-acid ligase that transfers the
CC gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting
CC in the formation of an activated acyl phosphate intermediate. This
CC intermediate is further hydrolyzed and the energy of hydrolysis is
CC utilized for the formation of the amide bond between actin subunits (By
CC similarity). {ECO:0000250|UniProtKB:Q9KS12,
CC ECO:0000269|PubMed:17873062, ECO:0000269|PubMed:20150509,
CC ECO:0000269|PubMed:26150500}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A0A0H3AIG7};
CC Note=Binds 2 Mg(2+) ions per subunit. Can also use Mn(2+) ions instead
CC of Mg(2+). {ECO:0000250|UniProtKB:A0A0H3AIG7};
CC -!- SUBUNIT: Interacts with protein VC1417. {ECO:0000269|PubMed:26150500}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17873062}. Host
CC cytoplasm, host cytosol {ECO:0000269|PubMed:17873062}. Note=Secreted
CC via the type VI secretion system. {ECO:0000269|PubMed:17873062}.
CC -!- DISRUPTION PHENOTYPE: Deletion leads to a loss of TseL secretion and in
CC turn loss of its ability to mediate prey cell killing.
CC {ECO:0000269|PubMed:20150509, ECO:0000269|PubMed:26150500}.
CC -!- SIMILARITY: Belongs to the VgrG protein family. {ECO:0000305}.
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DR EMBL; AE003852; AAF94573.1; -; Genomic_DNA.
DR PIR; D82202; D82202.
DR RefSeq; NP_231059.1; NC_002505.1.
DR RefSeq; WP_000212116.1; NZ_LT906614.1.
DR PDB; 4GQK; X-ray; 2.36 A; A=717-1111.
DR PDBsum; 4GQK; -.
DR AlphaFoldDB; Q9KS45; -.
DR SMR; Q9KS45; -.
DR STRING; 243277.VC_1416; -.
DR PRIDE; Q9KS45; -.
DR DNASU; 2614048; -.
DR EnsemblBacteria; AAF94573; AAF94573; VC_1416.
DR KEGG; vch:VC_1416; -.
DR PATRIC; fig|243277.26.peg.1345; -.
DR eggNOG; COG3501; Bacteria.
DR HOGENOM; CLU_008414_0_0_6; -.
DR BioCyc; VCHO:VC1416-MON; -.
DR Proteomes; UP000000584; Chromosome 1.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016881; F:acid-amino acid ligase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0030042; P:actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0090527; P:actin filament reorganization; IEA:InterPro.
DR GO; GO:0018262; P:isopeptide cross-linking; IDA:UniProtKB.
DR GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; ISS:UniProtKB.
DR Gene3D; 2.40.50.230; -; 1.
DR InterPro; IPR032074; ACD_dom.
DR InterPro; IPR006531; Gp5/Vgr_OB.
DR InterPro; IPR017847; T6SS_RhsGE_Vgr_subset.
DR InterPro; IPR006533; T6SS_Vgr_RhsGE.
DR InterPro; IPR037026; Vgr_OB-fold_dom_sf.
DR Pfam; PF16671; ACD; 1.
DR Pfam; PF04717; Phage_base_V; 1.
DR TIGRFAMs; TIGR01646; vgr_GE; 1.
DR TIGRFAMs; TIGR03361; VI_Rhs_Vgr; 1.
DR PROSITE; PS51772; ACD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Host cytoplasm; Ligase; Magnesium;
KW Metal-binding; Nucleotide-binding; Reference proteome; Secreted; Toxin;
KW Virulence.
FT CHAIN 1..1163
FT /note="Actin cross-linking toxin VgrG1"
FT /id="PRO_0000434120"
FT DOMAIN 728..1163
FT /note="ACD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01108"
FT BINDING 739..743
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:4GQK"
FT BINDING 743
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 743
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 805
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 808
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:4GQK"
FT BINDING 889
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 995
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 1066
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT STRAND 734..737
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 739..753
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 759..766
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 771..783
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 788..790
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 800..808
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 816..839
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 853..860
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 865..868
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 873..875
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 882..895
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 896..898
FT /evidence="ECO:0007829|PDB:4GQK"
FT TURN 899..901
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 905..911
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 920..927
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 929..931
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 936..960
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 969..972
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 978..980
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 984..990
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 991..994
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 998..1004
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 1007..1015
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 1017..1022
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 1027..1038
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 1043..1046
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 1052..1054
FT /evidence="ECO:0007829|PDB:4GQK"
FT STRAND 1056..1069
FT /evidence="ECO:0007829|PDB:4GQK"
FT HELIX 1072..1077
FT /evidence="ECO:0007829|PDB:4GQK"
SQ SEQUENCE 1163 AA; 128829 MW; FF95DFEC31FE9F15 CRC64;
MATLAYSIEV EGLEDETLVV RGFHGQESLS NSVFLGQACY GFRYEVQLAS RVSNLTAEQM
VDKRAELKLY RNSQLVQRVH GIVRAFSQGD IGHHHTFYQL TLVPALERLS LRHNSRIFQK
QTVPEILSIL LQEMGINDYA FALKRDGVQR EFCVQYRESD IDFLHRLAAE EGLVYSFVHE
AGKHTLYFSD ASDSLSKLPE PIPYNALVGG AIDTPYIHGL TYRTQAEVSE VQLKDYSFKK
PAYSFLQTVQ GTELDYQQTR YQHFDAPGRY KDDVNGAAFS QIRLDYLRRH AHTATGQSNE
PLLRAGYKFD LQEHLDPAMN RDWVVVSINH QGEQPQALQE DGGSGATTYS NQFSLIPGHL
HWRAEPQPKP QVDGPMIATV VGPEGEEIFC DEHGRVKIHF PWDRYSNGNE QSSCWVRVSQ
GWAGSQYGFI AIPRIGHEVI VEFLNGDPDQ PIITGRTYHA TNTPPYTLPE HKTKTVLRTE
THQGEGFNEL SFEDQAGKEQ IYLHAQKDFD GLIENDHTTV IRHDHHLTVE NDQFTQIKHN
QHLTVEWESR EAVTGEQVLS IEGSLHVKTG KVWVNEAGTE IHVKAGQKVV IEAGSEITVK
AGGSFVKVDP AGVHLSGALV NLNSGGSAGS GSGFGGAMPA LPGGLEPAVA LAPPQTISYQ
ALLQAEQANV PAVKVCPLAA QEATPAVNSI TPPPPPPIAP PMAPPQPIMN PQPTANAQPN
LGRSTKATPD FPTHFPKSSI GIENELAGLV VAMPANSAQK FGYVKSAQGD ALFMLTKDMN
QGSYQRPPSL QDGKNYQNWQ THTVELVSYP CEMDDKAAVE TRKQAMLWLA THFTTHIDQS
NHQPLAPIQS EDGRFVIEIT NAKHVIAAGN GISAESQGQT ITMTPSGQQA TVGVAAKGFG
TSATPELRLL ESAPWYQKSL KSQFASLTSA ENLDDKELAA NVFAYLTSIY LKTAELAKKF
GIYINEWDPM SEQITPNANG LTDPKVKNAW EILPRTKPSK IVEILSKSDA KAVMKHIKPQ
LQSRYSESLS KNVFQYFQDG GEVAGHGINN ATVGDKHSPE LAILFEFRTV PNELQSYLPK
TESTTKSEVK LLDQFDPMKR KTVIQQVESL VQNSGDAFDK WYQSYRDSMN QPPVKNAKKI
ASANQKAQWV KEHNPQEWQR IIA
