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| | ==Ebola virus VP24 structure== | | ==Ebola virus VP24 structure== |
| - | <StructureSection load='4m0q' size='340' side='right' caption='[[4m0q]], [[Resolution|resolution]] 1.92Å' scene=''> | + | <StructureSection load='4m0q' size='340' side='right'caption='[[4m0q]], [[Resolution|resolution]] 1.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m0q]] is a 2 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=4M0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M0Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m0q]] is a 2 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=4M0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M0Q FirstGlance]. <br> |
| - | </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=186538 ZEBOV])</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]] 1.921Å</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=4m0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0q RCSB], [http://www.ebi.ac.uk/pdbsum/4m0q PDBsum]</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=4m0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0q OCA], [https://pdbe.org/4m0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m0q RCSB], [https://www.ebi.ac.uk/pdbsum/4m0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0q ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP24_EBOZM VP24_EBOZM]] 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.<ref>PMID:12191476</ref> <ref>PMID:12525613</ref> <ref>PMID:15220407</ref> <ref>PMID:17928350</ref> | + | [https://www.uniprot.org/uniprot/VP24_EBOZM VP24_EBOZM] 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.<ref>PMID:12191476</ref> <ref>PMID:12525613</ref> <ref>PMID:15220407</ref> <ref>PMID:17928350</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4m0q" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[VP24|VP24]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Zebov]] | + | [[Category: Large Structures]] |
| - | [[Category: Amarasinghe, G K]] | + | [[Category: Zaire ebolavirus]] |
| - | [[Category: Borek, D]] | + | [[Category: Amarasinghe GK]] |
| - | [[Category: Leung, D W]] | + | [[Category: Borek D]] |
| - | [[Category: Xu, W]] | + | [[Category: Leung DW]] |
| - | [[Category: Ebola virus virulence factor]] | + | [[Category: Xu W]] |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
VP24_EBOZM 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.[1] [2] [3] [4]
Publication Abstract from PubMed
Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of either human or bat Keap1. This binding is of high affinity and 1:1 stoichiometry and activates Nrf2. Modeling based on the Zaire ebolavirus (EBOV) VP24 (eVP24) structure identified in mVP24 an acidic loop (K-loop) critical for Keap1 interaction. Transfer of the K-loop to eVP24, which otherwise does not bind Keap1, confers Keap1 binding and Nrf2 activation, and infection by MARV, but not EBOV, activates ARE gene expression. Therefore, MARV targets Keap1 to activate Nrf2-induced cytoprotective responses during infection.
The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway.,Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, Basler CF Cell Rep. 2014 Mar 27;6(6):1017-25. doi: 10.1016/j.celrep.2014.01.043. Epub 2014 , Mar 13. PMID:24630991[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang Y, Xu L, Sun Y, Nabel GJ. The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell. 2002 Aug;10(2):307-16. PMID:12191476
- ↑ Han Z, Boshra H, Sunyer JO, Zwiers SH, Paragas J, Harty RN. Biochemical and functional characterization of the Ebola virus VP24 protein: implications for a role in virus assembly and budding. J Virol. 2003 Feb;77(3):1793-800. PMID:12525613
- ↑ Licata JM, Johnson RF, Han Z, Harty RN. Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles. J Virol. 2004 Jul;78(14):7344-51. PMID:15220407 doi:http://dx.doi.org/10.1128/JVI.78.14.7344-7351.2004
- ↑ Reid SP, Valmas C, Martinez O, Sanchez FM, Basler CF. Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol. 2007 Dec;81(24):13469-77. Epub 2007 Oct 10. PMID:17928350 doi:http://dx.doi.org/10.1128/JVI.01097-07
- ↑ Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, Basler CF. The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway. Cell Rep. 2014 Mar 27;6(6):1017-25. doi: 10.1016/j.celrep.2014.01.043. Epub 2014 , Mar 13. PMID:24630991 doi:http://dx.doi.org/10.1016/j.celrep.2014.01.043
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