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| | ==Crystal structure of Marburg virus VP35 RNA binding domain bound to 12-bp dsRNA== | | ==Crystal structure of Marburg virus VP35 RNA binding domain bound to 12-bp dsRNA== |
| - | <StructureSection load='4gha' size='340' side='right' caption='[[4gha]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4gha' size='340' side='right'caption='[[4gha]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gha]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lake_victoria_marburgvirus_(strain_musoke-80) Lake victoria marburgvirus (strain musoke-80)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GHA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gha]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Marburg_virus_-_Musoke,_Kenya,_1980 Marburg virus - Musoke, Kenya, 1980]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GHA FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sk8|3sk8]], [[3fke|3fke]], [[3la2|3la2]], [[3l26|3l26]], [[3l25|3l25]], [[4gh9|4gh9]]</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]] 2.5Å</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=33727 Lake Victoria marburgvirus (strain Musoke-80)])</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=4gha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gha OCA], [https://pdbe.org/4gha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gha RCSB], [https://www.ebi.ac.uk/pdbsum/4gha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gha 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=4gha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gha OCA], [http://pdbe.org/4gha PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gha RCSB], [http://www.ebi.ac.uk/pdbsum/4gha PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gha ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP35_MABVM VP35_MABVM]] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. | + | [https://www.uniprot.org/uniprot/VP35_MABVM VP35_MABVM] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Filoviruses, including Marburg virus (MARV) and Ebola virus (EBOV), cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (ds)RNA-binding domain (RBD) of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules.
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| - | Marburg Virus VP35 Can Both Fully Coat the Backbone and Cap the Ends of dsRNA for Interferon Antagonism.,Bale S, Julien JP, Bornholdt ZA, Kimberlin CR, Halfmann P, Zandonatti MA, Kunert J, Kroon GJ, Kawaoka Y, Macrae IJ, Wilson IA, Saphire EO PLoS Pathog. 2012 Sep;8(9):e1002916. doi: 10.1371/journal.ppat.1002916. Epub 2012, Sep 13. PMID:23028316<ref>PMID:23028316</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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| - | <div class="pdbe-citations 4gha" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bale, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Bornholdt, Z A]] | + | [[Category: Marburg virus - Musoke, Kenya, 1980]] |
| - | [[Category: Halfmann, P]] | + | [[Category: Bale S]] |
| - | [[Category: Jean-Philippe, J]] | + | [[Category: Bornholdt ZA]] |
| - | [[Category: Kawaoka, Y]] | + | [[Category: Halfmann P]] |
| - | [[Category: Kimberlin, C K]] | + | [[Category: Jean-Philippe J]] |
| - | [[Category: Kroon, G J.A]] | + | [[Category: Kawaoka Y]] |
| - | [[Category: Kunert, J]] | + | [[Category: Kimberlin CK]] |
| - | [[Category: MacRae, I J]] | + | [[Category: Kroon GJA]] |
| - | [[Category: Saphire, E O]] | + | [[Category: Kunert J]] |
| - | [[Category: Wilson, I A]] | + | [[Category: MacRae IJ]] |
| - | [[Category: Zandonatti, M A]] | + | [[Category: Saphire EO]] |
| - | [[Category: Dsrna]]
| + | [[Category: Wilson IA]] |
| - | [[Category: Interferon inhibition]]
| + | [[Category: Zandonatti MA]] |
| - | [[Category: Rna binding protein-rna complex]]
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| - | [[Category: Viral polymerase]]
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| - | [[Category: Viral protein]]
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