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| | ==Crystal structure of Reston ebolavirus VP35 RNA binding domain in complex with 18bp dsRNA== | | ==Crystal structure of Reston ebolavirus VP35 RNA binding domain in complex with 18bp dsRNA== |
| - | <StructureSection load='3ks8' size='340' side='right' caption='[[3ks8]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3ks8' size='340' side='right'caption='[[3ks8]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ks8]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebore Ebore]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KS8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ks8]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Reston_ebolavirus_-_Reston Reston ebolavirus - Reston]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KS8 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ks4|3ks4]], [[3fke|3fke]]</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]] 2.401Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REBOVgp2, VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=129003 EBORE])</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=3ks8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ks8 OCA], [https://pdbe.org/3ks8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ks8 RCSB], [https://www.ebi.ac.uk/pdbsum/3ks8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ks8 ProSAT]</span></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=3ks8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ks8 OCA], [http://pdbe.org/3ks8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ks8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ks8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ks8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP35_EBORR VP35_EBORR]] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (By similarity). | + | [https://www.uniprot.org/uniprot/VP35_EBORR VP35_EBORR] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ks/3ks8_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ks/3ks8_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ebore]] | + | [[Category: Large Structures]] |
| - | [[Category: Bornholdt, Z A]] | + | [[Category: Reston ebolavirus - Reston]] |
| - | [[Category: Kimberlin, C R]]
| + | [[Category: Bornholdt ZA]] |
| - | [[Category: Li, S]]
| + | [[Category: Kimberlin CR]] |
| - | [[Category: Macrae, I J]]
| + | [[Category: Li S]] |
| - | [[Category: Saphire, E O]]
| + | [[Category: Macrae IJ]] |
| - | [[Category: Woods, V L]]
| + | [[Category: Saphire EO]] |
| - | [[Category: Ebolavirus]]
| + | [[Category: Woods VL]] |
| - | [[Category: Host cytoplasm]]
| + | |
| - | [[Category: Interferon]]
| + | |
| - | [[Category: Interferon antiviral system evasion]]
| + | |
| - | [[Category: Protein-rna complex]]
| + | |
| - | [[Category: Reston]]
| + | |
| - | [[Category: Rna replication]] | + | |
| - | [[Category: Rna-binding]] | + | |
| - | [[Category: Rna-binding protein]] | + | |
| - | [[Category: Transcription]] | + | |
| - | [[Category: Viral protein-rna complex]] | + | |
| - | [[Category: Virion]] | + | |
| Structural highlights
Function
VP35_EBORR Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ebolavirus causes a severe hemorrhagic fever and is divided into five distinct species, of which Reston ebolavirus is uniquely nonpathogenic to humans. Disease caused by ebolavirus is marked by early immunosuppression of innate immune signaling events, involving silencing and sequestration of double-stranded RNA (dsRNA) by the viral protein VP35. Here we present unbound and dsRNA-bound crystal structures of the dsRNA-binding domain of Reston ebolavirus VP35. The structures show that VP35 forms an unusual, asymmetric dimer on dsRNA binding, with each of the monomers binding dsRNA in a different way: one binds the backbone whereas the other caps the terminus. Additional SAXS, DXMS, and dsRNA-binding experiments presented here support a model of cooperative dsRNA recognition in which binding of the first monomer assists binding of the next monomer of the oligomeric VP35 protein. This work illustrates how ebolavirus VP35 could mask key recognition sites of molecules such as RIG-I, MDA-5, and Dicer to silence viral dsRNA in infection.
Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression.,Kimberlin CR, Bornholdt ZA, Li S, Woods VL Jr, Macrae IJ, Saphire EO Proc Natl Acad Sci U S A. 2009 Dec 14. PMID:20018665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kimberlin CR, Bornholdt ZA, Li S, Woods VL Jr, Macrae IJ, Saphire EO. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression. Proc Natl Acad Sci U S A. 2009 Dec 14. PMID:20018665
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