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| | ==Crystal Structure of the oligomerization domain of VP35 from Ebola virus, mercury derivative== | | ==Crystal Structure of the oligomerization domain of VP35 from Ebola virus, mercury derivative== |
| - | <StructureSection load='6gbp' size='340' side='right' caption='[[6gbp]], [[Resolution|resolution]] 3.49Å' scene=''> | + | <StructureSection load='6gbp' size='340' side='right'caption='[[6gbp]], [[Resolution|resolution]] 3.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gbp]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Zebov Zebov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gbp]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GBP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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]] 3.49Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186538 ZEBOV])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=6gbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbp OCA], [http://pdbe.org/6gbp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbp RCSB], [http://www.ebi.ac.uk/pdbsum/6gbp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbp 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=6gbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbp OCA], [https://pdbe.org/6gbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gbp RCSB], [https://www.ebi.ac.uk/pdbsum/6gbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts 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.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref> | + | [https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts 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.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref> |
| | <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: Zebov]] | + | [[Category: Large Structures]] |
| - | [[Category: Baumeister, W]] | + | [[Category: Zaire 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_EBOZM Acsts 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.[1] [2] [3] [4] [5]
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol. 1999 Mar;73(3):2333-42. PMID:9971816
- ↑ Basler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12289-94. PMID:11027311 doi:10.1073/pnas.220398297
- ↑ Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol. 2003 Jul;77(14):7945-56. PMID:12829834
- ↑ Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger E. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006 Mar;50(3):984-93. PMID:16495261 doi:10.1128/AAC.50.3.984-993.2006
- ↑ Feng Z, Cerveny M, Yan Z, He B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol. 2007 Jan;81(1):182-92. Epub 2006 Oct 25. PMID:17065211 doi:JVI.01006-06
- ↑ 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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