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| | ==Structure of poxvirus K7 protein in complex with RNA helicase DDX3== | | ==Structure of poxvirus K7 protein in complex with RNA helicase DDX3== |
| - | <StructureSection load='3jrv' size='340' side='right' caption='[[3jrv]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3jrv' size='340' side='right'caption='[[3jrv]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3jrv]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccw Vaccw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JRV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3jrv]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vaccinia_virus_WR Vaccinia virus WR]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JRV FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jrv OCA], [http://pdbe.org/3jrv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jrv RCSB], [http://www.ebi.ac.uk/pdbsum/3jrv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jrv ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3jrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jrv OCA], [https://pdbe.org/3jrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jrv RCSB], [https://www.ebi.ac.uk/pdbsum/3jrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jrv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/K7_VACCW K7_VACCW]] Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation. Contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation. [[http://www.uniprot.org/uniprot/DDX3X_HUMAN DDX3X_HUMAN]] Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo- and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double stranded DNA with a preference for 5'-single stranded DNA overhangs. Is involved in several steps of gene expression, such as transcription, mRNA maturation, mRNA export and translation. However, the exact mechanisms are not known and some functions may be specific for a subset of mRNAs. Involved in transcriptional regulation. Can enhance transcription from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found associated with the E-cadherin promoter and can down-regulate transcription from the promoter. Involved in regulation of translation initiation. Proposed to be involved in positive regulation of translation such as of cyclin E1/CCNE1 mRNA and specifically of mRNAs containing complex secondary structures in their 5'UTRs; these functions seem to require RNA helicase activity. Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. Proposed to act prior to 43S ribosomal scanning and to locally destabilize these RNA structures to allow recognition of the mRNA cap or loading onto the 40S subunit. After association with 40S ribosomal subunits seems to be involved in the functional assembly of 80S ribosomes; the function seems to cover translation of mRNAs with structured and non-structured 5'UTRs and is independent of RNA helicase activity. Also proposed to inhibit cap-dependent translation by competetive interaction with EIF4E which can block the EIF4E:EIF4G complex formation. Proposed to be involved in stress response and stress granule assembly; the function is independent of RNA helicase activity and seems to involve association with EIF4E. May be involved in nuclear export of specific mRNAs but not in bulk mRNA export via interactions with XPO1 and NXF1. Also associates with polyadenylated mRNAs independently of NXF1. Associates with spliced mRNAs in an exon junction complex (EJC)-dependent manner and seems not to be directly involved in splicing. May be involved in nuclear mRNA export by association with DDX5 and regulating its nuclear location. Involved in innate immune signaling promoting the production of type I interferon (IFN-alpha and IFN-beta); proposed to act as viral RNA sensor, signaling intermediate and transcriptional coactivator. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFN-beta induction. Also found associated with IFN-beta promoters; the function is independent of IRF3. Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Acts as an antiapoptotic protein through association with GSK3A/B and BIRC2 in an apoptosis antagonizing signaling complex; activation of death receptors promotes caspase-dependent cleavage of BIRC2 and DDX3X and relieves the inhibition. May be involved in mitotic chromosome segregation. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFN-beta induction probably by dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C virus (HCV) replication; the function may involve the association with HCV core protein. HCV core protein inhibits the IPS1-dependent function in viral RNA sensing and may switch the function from a INF-beta inducing to a HCV replication mode. Involved in HIV-1 replication. Acts as a cofactor for XPO1-mediated nuclear export of incompletely spliced HIV-1 Rev RNAs.<ref>PMID:10329544</ref> <ref>PMID:15507209</ref> <ref>PMID:16818630</ref> <ref>PMID:16301996</ref> <ref>PMID:17357160</ref> <ref>PMID:18846110</ref> <ref>PMID:18583960</ref> <ref>PMID:18636090</ref> <ref>PMID:18596238</ref> <ref>PMID:18628297</ref> <ref>PMID:17667941</ref> <ref>PMID:18264132</ref> <ref>PMID:20127681</ref> <ref>PMID:20375222</ref> <ref>PMID:20837705</ref> <ref>PMID:21170385</ref> <ref>PMID:20657822</ref> <ref>PMID:21589879</ref> <ref>PMID:21730191</ref> <ref>PMID:21883093</ref> <ref>PMID:22034099</ref> <ref>PMID:22323517</ref> <ref>PMID:22872150</ref> | + | [https://www.uniprot.org/uniprot/PG044_VACCW PG044_VACCW] Virulence factor that affects the acute immune response to infection (PubMed:23580427). Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation. Contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation.<ref>PMID:18636090</ref> <ref>PMID:19913487</ref> <ref>PMID:23580427</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3jrv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3jrv" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Helicase 3D structures|Helicase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vaccw]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Khan, R A]] | + | [[Category: Large Structures]] |
| - | [[Category: Oda, S]] | + | [[Category: Vaccinia virus WR]] |
| - | [[Category: Dead-box rna helicase ddx3]] | + | [[Category: Khan RA]] |
| - | [[Category: Innate immunity]] | + | [[Category: Oda S]] |
| - | [[Category: Poxvirus protein k7]]
| + | |
| - | [[Category: Viral immune evasion]]
| + | |
| - | [[Category: Viral protein-protein binding complex]]
| + | |
| Structural highlights
Function
PG044_VACCW Virulence factor that affects the acute immune response to infection (PubMed:23580427). Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation. Contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation.[1] [2] [3]
Publication Abstract from PubMed
Poxviruses are DNA viruses that express numerous proteins to subvert the host immune response. Vaccinia virus protein K7 adopts a Bcl-2 fold and displays structural and functional similarities to Toll-like receptor antagonist A52. Both proteins interact with IRAK2 and TRAF6 and suppress TLR-dependent NF-kappaB activation. However, unlike A52, K7 also forms a complex with RNA helicase DDX3 and antagonizes interferon-beta promoter induction. We have narrowed the K7 binding site to an N-terminal peptide motif of DDX3 ahead of its core RNA-helicase domains. The crystal structure of full-length K7 in complex with the DDX3 peptide reveals a thumblike projection of tandem phenalyalanine residues of DDX3 into a deep hydrophobic cleft. Mutagenesis of these phenylalanines abolishes the effects of DDX3 on interferon-beta promoter induction. The structure of K7-DDX3 reveals a novel binding mode by a viral Bcl-2 protein that antagonizes a key pathway in innate immunity.
Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7.,Oda S, Schroder M, Khan AR Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008 Aug 6;27(15):2147-57. doi: 10.1038/emboj.2008.143. Epub 2008 Jul 17. PMID:18636090 doi:http://dx.doi.org/10.1038/emboj.2008.143
- ↑ Oda S, Schroder M, Khan AR. Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487 doi:10.1016/j.str.2009.09.005
- ↑ Benfield CTO, Ren H, Lucas SJ, Bahsoun B, Smith GL. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection. J Gen Virol. 2013 Jul;94(Pt 7):1647-1657. PMID:23580427 doi:10.1099/vir.0.052670-0
- ↑ Oda S, Schroder M, Khan AR. Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure. 2009 Nov 11;17(11):1528-37. PMID:19913487 doi:10.1016/j.str.2009.09.005
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