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| | ==Structure of ebolavirus protein VP24 from Reston== | | ==Structure of ebolavirus protein VP24 from Reston== |
| - | <StructureSection load='4d9o' size='340' side='right' caption='[[4d9o]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4d9o' size='340' side='right'caption='[[4d9o]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4d9o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Reston_ebolavirus Reston ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D9O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D9O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4d9o]] is a 2 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=4D9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D9O FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vne|3vne]], [[3vnf|3vnf]]</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186539 Reston ebolavirus])</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=4d9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9o OCA], [https://pdbe.org/4d9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d9o RCSB], [https://www.ebi.ac.uk/pdbsum/4d9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d9o 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=4d9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d9o RCSB], [http://www.ebi.ac.uk/pdbsum/4d9o PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP24_EBORE VP24_EBORE]] Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. Blocks the IFN-induced nuclear accumulation of host phosphorylated STAT1, by interacting with the STAT1-binding region of host importin alpha-1/KPNA1 protein, thereby inhibiting the latter. Without the activity of this protein, activated STAT1 would not enter the nucleus and be unable to activate IFN-induced genes. Plays a role in assembly of viral nucleocapsid and virion budding. May act as a minor matrix protein that plays a role in assembly of viral nucleocapsid and virion budding. | + | [https://www.uniprot.org/uniprot/VP24_EBORE VP24_EBORE] Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. Blocks the IFN-induced nuclear accumulation of host phosphorylated STAT1, by interacting with the STAT1-binding region of host importin alpha-1/KPNA1 protein, thereby inhibiting the latter. Without the activity of this protein, activated STAT1 would not enter the nucleus and be unable to activate IFN-induced genes. Plays a role in assembly of viral nucleocapsid and virion budding. May act as a minor matrix protein that plays a role in assembly of viral nucleocapsid and virion budding. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. One of the proteins likely responsible for this effect is VP24. VP24 is known to antagonize interferon signaling by binding host karyopherin alpha proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1 directly, suggesting that VP24 can suppress at least two distinct branches of the interferon pathway. Here, we also report the first crystal structures of VP24, derived from different species of ebolavirus that are pathogenic (Sudan) and nonpathogenic to humans (Reston). These structures reveal that VP24 has a novel, pyramidal fold. A site on a particular face of the pyramid exhibits reduced solvent exchange when in complex with STAT1. This site is above two highly conserved pockets in VP24 that contain key residues previously implicated in virulence. These crystal structures and accompanying biochemical analysis map differences between pathogenic and nonpathogenic viruses, offer templates for drug design, and provide the three-dimensional framework necessary for biological dissection of the many functions of VP24 in the virus life cycle.
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| - | The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold.,Zhang AP, Bornholdt ZA, Liu T, Abelson DM, Lee DE, Li S, Woods VL Jr, Saphire EO PLoS Pathog. 2012 Feb;8(2):e1002550. Epub 2012 Feb 23. PMID:22383882<ref>PMID:22383882</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | ==See Also== | | ==See Also== |
| | *[[VP24|VP24]] | | *[[VP24|VP24]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Reston ebolavirus]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, A P.P]]
| + | [[Category: Reston ebolavirus - Reston]] |
| - | [[Category: Ebolavirus]]
| + | [[Category: Zhang APP]] |
| - | [[Category: Ifn response pathway]]
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| - | [[Category: Interferon antagonist]]
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| - | [[Category: Karyopherin alpha]]
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| - | [[Category: Reston]] | + | |
| - | [[Category: Stat1]] | + | |
| - | [[Category: Sudan]]
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| - | [[Category: Viral protein]]
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| - | [[Category: Vp24]]
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| - | [[Category: Vp35]]
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| - | [[Category: Zaire]]
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