VGRG1_VIBC3
ID VGRG1_VIBC3 Reviewed; 1095 AA.
AC A0A0H3AIG7;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Actin cross-linking toxin VgrG1 {ECO:0000305};
DE EC=6.3.2.- {ECO:0000305|PubMed:22898822};
GN Name=vgrG1 {ECO:0000303|PubMed:22898822};
GN Synonyms=vgrG-1 {ECO:0000312|EMBL:ABQ19866.1};
GN OrderedLocusNames=VC0395_A1026 {ECO:0000312|EMBL:ABQ19866.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39541 / Classical Ogawa 395 /
OS O395).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=345073;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39541 / Classical Ogawa 395 / O395
RC {ECO:0000312|Proteomes:UP000000249};
RA Heidelberg J.;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39541 / Classical Ogawa 395 / O395;
RX PubMed=19115014; DOI=10.1371/journal.pone.0004053;
RA Feng L., Reeves P.R., Lan R., Ren Y., Gao C., Zhou Z., Ren Y., Cheng J.,
RA Wang W., Wang J., Qian W., Li D., Wang L.;
RT "A recalibrated molecular clock and independent origins for the cholera
RT pandemic clones.";
RL PLoS ONE 3:E4053-E4053(2008).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 700-1095 IN COMPLEX WITH ATP AND
RP MAGNESIUM, FUNCTION, COFACTOR, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-727.
RX PubMed=22898822; DOI=10.1074/jbc.m112.390153;
RA Durand E., Derrez E., Audoly G., Spinelli S., Ortiz-Lombardia M.,
RA Raoult D., Cascales E., Cambillau C.;
RT "Crystal structure of the VgrG1 actin cross-linking domain of the Vibrio
RT cholerae type VI secretion system.";
RL J. Biol. Chem. 287:38190-38199(2012).
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 (By similarity).
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 (By
CC similarity). 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:22898822). The
CC toxin can be highly efficient at very low concentrations by acting on
CC formin homology family proteins: toxic actin oligomers bind with high
CC affinity to formins and adversely affect both nucleation and elongation
CC abilities of formins, causing their potent inhibition in both profilin-
CC dependent and independent manners (PubMed:22898822). Acts as an acid--
CC amino-acid ligase that transfers the gamma-phosphoryl group of ATP to
CC the 'Glu-270' actin residue, resulting in the formation of an activated
CC acyl phosphate intermediate. This intermediate is further hydrolyzed
CC and the energy of hydrolysis is utilized for the formation of the amide
CC bond between actin subunits (PubMed:22898822).
CC {ECO:0000250|UniProtKB:Q9KS45, ECO:0000269|PubMed:22898822}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22898822};
CC Note=Binds 2 Mg(2+) ions per subunit. Can also use Mn(2+) ions instead
CC of Mg(2+). {ECO:0000269|PubMed:22898822};
CC -!- SUBUNIT: Interacts with protein VC1417. {ECO:0000250|UniProtKB:Q9KS45}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9KS45}. Host
CC cytoplasm, host cytosol {ECO:0000269|PubMed:22898822}. Note=Secreted
CC via the type VI secretion system. {ECO:0000250|UniProtKB:Q9KS45}.
CC -!- SIMILARITY: Belongs to the VgrG protein family. {ECO:0000305}.
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DR EMBL; CP000627; ABQ19866.1; -; Genomic_DNA.
DR EMBL; CP001235; ACP09541.1; -; Genomic_DNA.
DR RefSeq; WP_000212118.1; NZ_JAACZH010000030.1.
DR PDB; 4DTD; X-ray; 2.50 A; A=700-1095.
DR PDB; 4DTF; X-ray; 2.12 A; A=700-1095.
DR PDB; 4DTH; X-ray; 1.78 A; A=700-1095.
DR PDB; 4DTL; X-ray; 2.39 A; A=701-1095.
DR PDB; 4E1C; X-ray; 2.25 A; A=700-1095.
DR PDB; 4E1D; X-ray; 2.49 A; A=700-1095.
DR PDB; 4E1F; X-ray; 2.10 A; A=700-1095.
DR PDBsum; 4DTD; -.
DR PDBsum; 4DTF; -.
DR PDBsum; 4DTH; -.
DR PDBsum; 4DTL; -.
DR PDBsum; 4E1C; -.
DR PDBsum; 4E1D; -.
DR PDBsum; 4E1F; -.
DR AlphaFoldDB; A0A0H3AIG7; -.
DR SMR; A0A0H3AIG7; -.
DR STRING; 345073.VC395_1535; -.
DR EnsemblBacteria; ABQ19866; ABQ19866; VC0395_A1026.
DR KEGG; vco:VC0395_A1026; -.
DR KEGG; vcr:VC395_1535; -.
DR PATRIC; fig|345073.21.peg.1485; -.
DR eggNOG; COG3501; Bacteria.
DR HOGENOM; CLU_008414_0_0_6; -.
DR Proteomes; UP000000249; Chromosome 2.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA: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:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; IDA: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; Secreted; Toxin; Virulence.
FT CHAIN 1..1095
FT /note="Actin cross-linking toxin VgrG1"
FT /id="PRO_0000434119"
FT DOMAIN 712..1095
FT /note="ACD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01108"
FT BINDING 723..727
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1C, ECO:0007744|PDB:4E1D,
FT ECO:0007744|PDB:4E1F"
FT BINDING 727
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:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1D"
FT BINDING 727
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:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1D"
FT BINDING 789
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:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1D"
FT BINDING 792
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTF, ECO:0007744|PDB:4DTH,
FT ECO:0007744|PDB:4DTL, ECO:0007744|PDB:4E1C,
FT ECO:0007744|PDB:4E1D, ECO:0007744|PDB:4E1F"
FT BINDING 873
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:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1D"
FT BINDING 979
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4E1D"
FT BINDING 1050
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:0000269|PubMed:22898822,
FT ECO:0007744|PDB:4DTH, ECO:0007744|PDB:4DTL,
FT ECO:0007744|PDB:4E1D"
FT MUTAGEN 727
FT /note="E->Q: Abolished actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:22898822"
FT STRAND 718..721
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 723..729
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 731..737
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 743..750
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 755..767
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 772..774
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 784..792
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 800..823
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 837..844
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 849..852
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 857..859
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 869..871
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 872..879
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 880..882
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 889..895
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 904..911
FT /evidence="ECO:0007829|PDB:4DTH"
FT TURN 912..914
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 920..944
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 953..956
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 962..964
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 968..974
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 975..978
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 982..988
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 991..1006
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 1011..1022
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 1027..1030
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 1036..1039
FT /evidence="ECO:0007829|PDB:4DTH"
FT STRAND 1042..1053
FT /evidence="ECO:0007829|PDB:4DTH"
FT HELIX 1056..1061
FT /evidence="ECO:0007829|PDB:4DTH"
SQ SEQUENCE 1095 AA; 120779 MW; 3419E1AF253018FB 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 GLIENDQFTQ IKHNQHLTVE WESREAVTGE
QVLSIEGSLH VKTGKVRVNE AGTEIHVKAG QKVVIEAGSE ITVKAGGSFV KVDPAGVHLS
GALVNLNSGG SAGSGSGFGG AMPALPGGLE PAVALAPPQT ISYQALLQAE QANVPAVKVC
PLAAQEATPA VNSITPPPPP PIAPPMAPPQ PIMNPQPTAN AQPNLGRSTK ATPDFPTHFP
KSSIGIENEL AGLVVAMPAN SAQKFGYVKS AQGDALFMLT KDMNQGSYQR PPSLQDGKNY
QNWQTHTVEL VSYPCEMDDK AAVETRKQAM LWLATHFTTH IDQSNHQPLA PIQSEDGRFV
IEITNAKHVI AAGNGISAES QGQTITMTPS GQQATVGVAA KGFGTSATPE LRLLESAPWY
QKSLKSQFAS LTSAENLDDK ELAANVFAYL TSIYLKTAEL AKKFGIYINE WDPMSEQITP
NANGLTDPKV KNAWEILPRT KPSKIVEILS KSDAKAVMKH IKPQLQSRYS ESLSKNVFQY
FQDGGEVAGH GINNATVGDK HSPELAILFE FRTVPNELQS YLPKTESTTK SEVKLLDQFD
PMKRKTVIQQ VESLV
