VP35_EBORR
ID VP35_EBORR Reviewed; 329 AA.
AC Q8JPY0;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 82.
DE RecName: Full=Polymerase cofactor VP35;
GN Name=VP35; ORFNames=REBOVgp2;
OS Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=386032;
OH NCBI_TaxID=77231; Epomops franqueti (Franquet's epauleted fruit bat).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12191779; DOI=10.1016/s0168-1702(02)00087-4;
RA Groseth A., Stroeher U., Theriault S., Feldmann H.;
RT "Molecular characterization of an isolate from the 1989/90 epizootic of
RT Ebola virus Reston among macaques imported into the United States.";
RL Virus Res. 87:155-163(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Pennsylvania-89;
RX PubMed=15661171; DOI=10.1016/j.virol.2004.11.018;
RA Boehmann Y., Enterlein S., Randolf A., Muehlberger E.I.;
RT "A reconstituted replication and transcription system for Ebola virus
RT Reston and comparison with Ebola virus Zaire.";
RL Virology 332:406-417(2005).
RN [3] {ECO:0007744|PDB:3L2A}
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 204-329, AND DOMAIN.
RX PubMed=20399790; DOI=10.1016/j.jmb.2010.04.022;
RA Leung D.W., Shabman R.S., Farahbakhsh M., Prins K.C., Borek D.M., Wang T.,
RA Muhlberger E., Basler C.F., Amarasinghe G.K.;
RT "Structural and functional characterization of Reston Ebola virus VP35
RT interferon inhibitory domain.";
RL J. Mol. Biol. 399:347-357(2010).
RN [4] {ECO:0007744|PDB:3KS4, ECO:0007744|PDB:3KS8}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 160-329, SUBUNIT, FUNCTION,
RP RNA-BINDING, AND DOMAIN.
RX PubMed=20018665; DOI=10.1073/pnas.0910547107;
RA Kimberlin C.R., Bornholdt Z.A., Li S., Woods V.L. Jr., MacRae I.J.,
RA Saphire E.O.;
RT "Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune
RT suppression.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:314-319(2010).
RN [5] {ECO:0007744|PDB:4LG2}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 205-329, RNA-BINDING, AND DOMAIN.
RX PubMed=23824825; DOI=10.1128/jvi.01452-13;
RA Bale S., Julien J.P., Bornholdt Z.A., Krois A.S., Wilson I.A.,
RA Saphire E.O.;
RT "Ebolavirus VP35 coats the backbone of double-stranded RNA for interferon
RT antagonism.";
RL J. Virol. 87:10385-10388(2013).
RN [6] {ECO:0007744|PDB:6GBQ, ECO:0007744|PDB:6GBR}
RP X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) OF 71-134, AND SUBUNIT.
RX PubMed=30482729; DOI=10.1016/j.str.2018.09.009;
RA Zinzula L., Nagy I., Orsini M., Weyher-Stingl E., Bracher A.,
RA Baumeister W.;
RT "Structures of Ebola and Reston Virus VP35 Oligomerization Domains and
RT Comparative Biophysical Characterization in All Ebolavirus Species.";
RL Structure 27:39-54.e6(2019).
CC -!- FUNCTION: Plays an essential role in viral RNA synthesis and also a
CC role in suppressing innate immune signaling. Acts as a polymerase
CC cofactor in the RNA polymerase transcription and replication complexes
CC (By similarity). Serves as nucleoprotein/NP monomer chaperone prior to
CC the formation of the large oligomeric RNA-bound complexes (By
CC similarity). Regulates RNA synthesis by modulating NP-RNA interactions
CC and interacting with DYNLL1. VP35-NP interaction controls the switch
CC between RNA-bound NP and free NP and thus the switch between genome
CC replication and genome packaging into the nucleocapsid. Prevents
CC establishment of cellular antiviral state, thereby suppressing host DC
CC maturation. Acts by inhibiting host DDX58/RIG-I activation both by
CC shielding dsRNA from detection and by preventing PRKRA binding to
CC DDX58. Blocks virus-induced phosphorylation and activation of
CC interferon regulatory factor 3/IRF3, a transcription factor critical
CC for the induction of interferons alpha and beta. This blockage is
CC produced through the interaction with and inhibition of host IKBKE and
CC TBK1, producing a strong inhibition of the phosphorylation and
CC activation of IRF3. Also inhibits the antiviral effect mediated by the
CC host interferon-induced, double-stranded RNA-activated protein kinase
CC EIF2AK2/PKR. Increases PIAS1-mediated SUMOylation of IRF7, thereby
CC repressing interferon transcription (By similarity). Also acts as a
CC suppressor of RNA silencing by interacting with host DICER1,
CC TARBP2/TRBP and PRKRA/PACT (By similarity). As a dimer, binds and
CC sequesters dsRNA contributing to the inhibition of interferon
CC production (PubMed:20018665). {ECO:0000250|UniProtKB:Q05127,
CC ECO:0000250|UniProtKB:Q5XX07, ECO:0000250|UniProtKB:Q6V1Q9,
CC ECO:0000269|PubMed:20018665}.
CC -!- SUBUNIT: Homodimer (PubMed:20018665). Homooligomer; via the coiled coil
CC domain (PubMed:30482729). Interacts with nucleoprotein NP and
CC polymerase L; VP35 bridges L and NP and allows the formation of the
CC polymerase complex. Also interacts with VP30; this interaction is
CC regulated by VP30 phosphorylation. Interacts with host IKBKE and TBK1;
CC the interactions lead to inhibition of cellular antiviral response by
CC blocking necessary interactions of IKBKE and TBK1 with their substrate
CC IRF3. Interacts with host DYNLL1; this interaction stabilizes VP35 N-
CC terminal oligomerization domain, enhances viral RNA synthesis but does
CC not participate in suppressing the host innate immune response.
CC Interacts with host PRKRA; this interaction inhibits the interaction
CC between DDX58 and PRKRA. Interacts with dsRNA. Interacts with host
CC TRIM6; this interaction plays an important role in promoting efficient
CC viral replication. Interacts with host STAU1. Interacts with host IRF7,
CC PIAS1 and UBE2I/UBC9; these interactions mediate the sumoylation of
CC IRF7 and contribute to the inhibition of IFN-type I production (By
CC similarity). Interacts with host DICER1; this interaction prevents
CC TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract
CC host RNA silencing. Interacts with host TARBP2/TRBP and PRKRA/PACT;
CC these interactions prevent TARBP2 and PRKRA binding to DICER1 and thus
CC allows the virus to counteract host RNA silencing (By similarity).
CC {ECO:0000250|UniProtKB:Q05127, ECO:0000250|UniProtKB:Q6V1Q9,
CC ECO:0000269|PubMed:20018665, ECO:0000269|PubMed:30482729}.
CC -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm {ECO:0000250}.
CC -!- DOMAIN: The interferon inhibitory domain (IID) binds dsRNA.
CC {ECO:0000269|PubMed:20018665, ECO:0000269|PubMed:20399790,
CC ECO:0000269|PubMed:23824825}.
CC -!- PTM: Phosphorylated by host IKBKE. Phosphorylation contributes to
CC efficient viral replication and transcription.
CC {ECO:0000250|UniProtKB:Q05127}.
CC -!- SIMILARITY: Belongs to the filoviridae polymerase cofactor VP35 family.
CC {ECO:0000255|PROSITE-ProRule:PRU01071}.
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DR EMBL; AF522874; AAN04449.1; -; Genomic_RNA.
DR EMBL; AY769362; AAV48575.1; -; Genomic_RNA.
DR RefSeq; NP_690581.1; NC_004161.1.
DR PDB; 3KS4; X-ray; 2.40 A; A/B=160-329.
DR PDB; 3KS8; X-ray; 2.40 A; A/B/C/D=160-329.
DR PDB; 3L2A; X-ray; 1.71 A; A=204-329.
DR PDB; 4LG2; X-ray; 2.70 A; A/B/C/D=205-329.
DR PDB; 6GBQ; X-ray; 2.43 A; A/B/C/D/E/F/G/H=71-134.
DR PDB; 6GBR; X-ray; 3.15 A; A/B/C/D=71-134.
DR PDBsum; 3KS4; -.
DR PDBsum; 3KS8; -.
DR PDBsum; 3L2A; -.
DR PDBsum; 4LG2; -.
DR PDBsum; 6GBQ; -.
DR PDBsum; 6GBR; -.
DR SMR; Q8JPY0; -.
DR GeneID; 955189; -.
DR KEGG; vg:955189; -.
DR EvolutionaryTrace; Q8JPY0; -.
DR Proteomes; UP000007207; Genome.
DR Proteomes; UP000138664; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039724; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IKBKE activity; IEA:UniProtKB-KW.
DR GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
DR GO; GO:0039723; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.8.950; -; 1.
DR Gene3D; 2.10.10.70; -; 1.
DR InterPro; IPR002953; Filo_VP35.
DR InterPro; IPR031163; VP35_IID.
DR InterPro; IPR043061; VP35_IID_b-sht.
DR InterPro; IPR043060; VP35_IID_hlx.
DR Pfam; PF02097; Filo_VP35; 1.
DR PIRSF; PIRSF018326; VP35_FiloV; 1.
DR PRINTS; PR01240; FILOVP35.
DR PROSITE; PS51735; VP35_IID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Host cytoplasm; Host-virus interaction;
KW Inhibition of host IKBKE by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host IRF7 by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host TBK1 by virus; Inhibition of host TLR pathway by virus;
KW Interferon antiviral system evasion; Phosphoprotein; RNA-binding;
KW Suppressor of RNA silencing; Transcription; Viral immunoevasion;
KW Viral RNA replication; Virion.
FT CHAIN 1..329
FT /note="Polymerase cofactor VP35"
FT /id="PRO_0000245076"
FT DOMAIN 204..329
FT /note="VP35 IID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01071,
FT ECO:0000269|PubMed:23824825"
FT REGION 83..145
FT /note="Homooligomerization"
FT /evidence="ECO:0000269|PubMed:30482729"
FT COILED 84..112
FT /evidence="ECO:0000255"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 199
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT HELIX 73..134
FT /evidence="ECO:0007829|PDB:6GBQ"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:3L2A"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 227..241
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 245..257
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:3L2A"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:3L2A"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:3L2A"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:3L2A"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:3L2A"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:3L2A"
SQ SEQUENCE 329 AA; 36410 MW; 398BA99B4603C5CC CRC64;
MYNNKLKVCS GPETTGWISE QLMTGKIPVT DIFIDIDNKP DQMEVRLKPS SRSSTRTCTS
SSQTEVNYVP LLKKVEDTLT MLVNATSRQN AAIEALENRL STLESSLKPI QDMGKVISSL
NRSCAEMVAK YDLLVMTTGR ATSTAAAVDA YWKEHKQPPP GPALYEENAL KGKIDDPNSY
VPDAVQEAYK NLDSTSTLTE ENFGKPYISA KDLKEIMYDH LPGFGTAFHQ LVQVICKIGK
DNNLLDTIHA EFQASLADGD SPQCALIQIT KRVPIFQDVP PPIIHIRSRG DIPRACQKSL
RPAPPSPKID RGWVCLFKMQ DGKTLGLKI
