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| | ==Crystal Structure of the oligomerization domain of VP35 from Reston virus, mercury derivative== | | ==Crystal Structure of the oligomerization domain of VP35 from Reston virus, mercury derivative== |
| - | <StructureSection load='6gbr' size='340' side='right' caption='[[6gbr]], [[Resolution|resolution]] 3.15Å' scene=''> | + | <StructureSection load='6gbr' size='340' side='right'caption='[[6gbr]], [[Resolution|resolution]] 3.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gbr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebola_virus_reston Ebola virus reston]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gbr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Reston_ebolavirus Reston ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GBR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MBO:MERCURIBENZOIC+ACID'>MBO</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]] 3.15Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP35, REBOVgp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186539 Ebola virus Reston])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MBO:MERCURIBENZOIC+ACID'>MBO</scene></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=6gbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbr OCA], [http://pdbe.org/6gbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbr RCSB], [http://www.ebi.ac.uk/pdbsum/6gbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbr ProSAT]</span></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=6gbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbr OCA], [https://pdbe.org/6gbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gbr RCSB], [https://www.ebi.ac.uk/pdbsum/6gbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbr 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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ebola virus reston]] | + | [[Category: Large Structures]] |
| - | [[Category: Baumeister, W]] | + | [[Category: Reston ebolavirus]] |
| - | [[Category: Bracher, A]] | + | [[Category: Baumeister W]] |
| - | [[Category: Nagy, I]] | + | [[Category: Bracher A]] |
| - | [[Category: Orsini, M]] | + | [[Category: Nagy I]] |
| - | [[Category: Weyher-Stingl, E]] | + | [[Category: Orsini M]] |
| - | [[Category: Zinzula, L]] | + | [[Category: Weyher-Stingl E]] |
| - | [[Category: Coiled-coil]]
| + | [[Category: Zinzula L]] |
| - | [[Category: Viral protein]]
| + | |
| 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).
Publication Abstract from PubMed
The multifunctional virion protein 35 (VP35) of ebolaviruses is a critical determinant of virulence and pathogenesis indispensable for viral replication and host innate immune evasion. Essential for VP35 function is homo-oligomerization via a coiled-coil motif. Here we report crystal structures of VP35 oligomerization domains from the prototypic Ebola virus (EBOV) and the non-pathogenic Reston virus (RESTV), together with a comparative biophysical characterization of the domains from all known species of the Ebolavirus genus. EBOV and RESTV VP35 oligomerization domains form bipartite parallel helix bundles with a canonical coiled coil in the N-terminal half and increased plasticity in the highly conserved C-terminal half. The domain assembles into trimers and tetramers in EBOV, whereas it exclusively forms tetramers in all other ebolavirus species. Substitution of coiled-coil leucine residues critical for immune antagonism leads to aberrant oligomerization. A conserved arginine involved in inter-chain salt bridges stabilizes the VP35 oligomerization domain and modulates between coiled-coil oligomeric states.
Structures of Ebola and Reston Virus VP35 Oligomerization Domains and Comparative Biophysical Characterization in All Ebolavirus Species.,Zinzula L, Nagy I, Orsini M, Weyher-Stingl E, Bracher A, Baumeister W Structure. 2018 Oct 5. pii: S0969-2126(18)30335-6. doi:, 10.1016/j.str.2018.09.009. PMID:30482729[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zinzula L, Nagy I, Orsini M, Weyher-Stingl E, Bracher A, Baumeister W. Structures of Ebola and Reston Virus VP35 Oligomerization Domains and Comparative Biophysical Characterization in All Ebolavirus Species. Structure. 2018 Oct 5. pii: S0969-2126(18)30335-6. doi:, 10.1016/j.str.2018.09.009. PMID:30482729 doi:http://dx.doi.org/10.1016/j.str.2018.09.009
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