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| | ==Structural Basis for Marburg virus VP35 mediate immune evasion mechanisms== | | ==Structural Basis for Marburg virus VP35 mediate immune evasion mechanisms== |
| - | <StructureSection load='4ghl' size='340' side='right' caption='[[4ghl]], [[Resolution|resolution]] 2.02Å' scene=''> | + | <StructureSection load='4ghl' size='340' side='right'caption='[[4ghl]], [[Resolution|resolution]] 2.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ghl]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lake_victoria_marburg_virus_-_popp Lake victoria marburg virus - popp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GHL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GHL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ghl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lake_Victoria_marburgvirus_-_Popp Lake Victoria marburgvirus - Popp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GHL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fke|3fke]], [[3l25|3l25]], [[3l26|3l26]], [[3l27|3l27]], [[3l28|3l28]], [[3l29|3l29]]</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=4ghl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ghl OCA], [https://pdbe.org/4ghl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ghl RCSB], [https://www.ebi.ac.uk/pdbsum/4ghl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ghl ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Polymerase cofactor VP35, VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33728 Lake Victoria marburg virus - Popp])</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=4ghl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ghl OCA], [http://pdbe.org/4ghl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ghl RCSB], [http://www.ebi.ac.uk/pdbsum/4ghl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ghl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP35_MABVP VP35_MABVP]] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. | + | [https://www.uniprot.org/uniprot/VP35_MABVP VP35_MABVP] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. |
| | <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: Lake victoria marburg virus - popp]] | + | [[Category: Lake Victoria marburgvirus - Popp]] |
| - | [[Category: Amarasinghe, G K]] | + | [[Category: Large Structures]] |
| - | [[Category: Borek, D M]] | + | [[Category: Amarasinghe GK]] |
| - | [[Category: Leung, D W]] | + | [[Category: Borek DM]] |
| - | [[Category: Otwinowski, Z]] | + | [[Category: Leung DW]] |
| - | [[Category: Ramanan, P]] | + | [[Category: Otwinowski Z]] |
| - | [[Category: Double stranded rna]]
| + | [[Category: Ramanan P]] |
| - | [[Category: Ifn inhibitor]]
| + | |
| - | [[Category: Interferon antagonism]]
| + | |
| - | [[Category: Protein-rna complex]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Viral protein-rna complex]]
| + | |
| - | [[Category: Vp35]]
| + | |
| Structural highlights
Function
VP35_MABVP Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex.
Publication Abstract from PubMed
Filoviruses, marburgvirus (MARV) and ebolavirus (EBOV), are causative agents of highly lethal hemorrhagic fever in humans. MARV and EBOV share a common genome organization but show important differences in replication complex formation, cell entry, host tropism, transcriptional regulation, and immune evasion. Multifunctional filoviral viral protein (VP) 35 proteins inhibit innate immune responses. Recent studies suggest double-stranded (ds)RNA sequestration is a potential mechanism that allows EBOV VP35 to antagonize retinoic-acid inducible gene-I (RIG-I) like receptors (RLRs) that are activated by viral pathogen-associated molecular patterns (PAMPs), such as double-strandedness and dsRNA blunt ends. Here, we show that MARV VP35 can inhibit IFN production at multiple steps in the signaling pathways downstream of RLRs. The crystal structure of MARV VP35 IID in complex with 18-bp dsRNA reveals that despite the similar protein fold as EBOV VP35 IID, MARV VP35 IID interacts with the dsRNA backbone and not with blunt ends. Functional studies show that MARV VP35 can inhibit dsRNA-dependent RLR activation and interferon (IFN) regulatory factor 3 (IRF3) phosphorylation by IFN kinases TRAF family member-associated NFkb activator (TANK) binding kinase-1 (TBK-1) and IFN kB kinase e (IKKe) in cell-based studies. We also show that MARV VP35 can only inhibit RIG-I and melanoma differentiation associated gene 5 (MDA5) activation by double strandedness of RNA PAMPs (coating backbone) but is unable to inhibit activation of RLRs by dsRNA blunt ends (end capping). In contrast, EBOV VP35 can inhibit activation by both PAMPs. Insights on differential PAMP recognition and inhibition of IFN induction by a similar filoviral VP35 fold, as shown here, reveal the structural and functional plasticity of a highly conserved virulence factor.
Structural basis for Marburg virus VP35-mediated immune evasion mechanisms.,Ramanan P, Edwards MR, Shabman RS, Leung DW, Endlich-Frazier AC, Borek DM, Otwinowski Z, Liu G, Huh J, Basler CF, Amarasinghe GK Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20661-6. doi:, 10.1073/pnas.1213559109. Epub 2012 Nov 26. PMID:23185024[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ramanan P, Edwards MR, Shabman RS, Leung DW, Endlich-Frazier AC, Borek DM, Otwinowski Z, Liu G, Huh J, Basler CF, Amarasinghe GK. Structural basis for Marburg virus VP35-mediated immune evasion mechanisms. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20661-6. doi:, 10.1073/pnas.1213559109. Epub 2012 Nov 26. PMID:23185024 doi:http://dx.doi.org/10.1073/pnas.1213559109
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