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| | ==Crystal structure of bat influenza A/H17N10 polymerase with viral RNA promoter and capped RNA primer== | | ==Crystal structure of bat influenza A/H17N10 polymerase with viral RNA promoter and capped RNA primer== |
| - | <StructureSection load='6evj' size='340' side='right' caption='[[6evj]], [[Resolution|resolution]] 3.90Å' scene=''> | + | <StructureSection load='6evj' size='340' side='right'caption='[[6evj]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6evj]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/little_yellow-shouldered_bat/guatemala/060/2010(h17n10)) Influenza a virus (a/little yellow-shouldered bat/guatemala/060/2010(h17n10))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6evj]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/little_yellow-shouldered_bat/Guatemala/060/2010(H17N10)) Influenza A virus (A/little yellow-shouldered bat/Guatemala/060/2010(H17N10))] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EVJ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8NK:7-METHYLGUANOSINE+5-DIPHOSPHATE'>8NK</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]] 3.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1129347 Influenza A virus (A/little yellow-shouldered bat/Guatemala/060/2010(H17N10))]), PB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1129347 Influenza A virus (A/little yellow-shouldered bat/Guatemala/060/2010(H17N10))]), PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1129347 Influenza A virus (A/little yellow-shouldered bat/Guatemala/060/2010(H17N10))])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8NK:7-METHYLGUANOSINE+5-DIPHOSPHATE'>8NK</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=6evj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evj OCA], [https://pdbe.org/6evj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6evj RCSB], [https://www.ebi.ac.uk/pdbsum/6evj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6evj 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=6evj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evj OCA], [http://pdbe.org/6evj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evj RCSB], [http://www.ebi.ac.uk/pdbsum/6evj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/H6QM92_9INFA H6QM92_9INFA] |
| - | Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation ('priming state') and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the 'apo' state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the 'apo' state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive 'apo' state.
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| - | Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors.,Pflug A, Gaudon S, Resa-Infante P, Lethier M, Reich S, Schulze WM, Cusack S Nucleic Acids Res. 2017 Nov 30. pii: 4675317. doi: 10.1093/nar/gkx1210. PMID:29202182<ref>PMID:29202182</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 6evj" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[End-binding protein|End-binding protein]] |
| - | == References ==
| + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: RNA-directed RNA polymerase]] | + | [[Category: Influenza A virus]] |
| - | [[Category: Cusack, S]]
| + | [[Category: Large Structures]] |
| - | [[Category: Pflug, A]]
| + | [[Category: Synthetic construct]] |
| - | [[Category: Capped rna primer]] | + | [[Category: Cusack S]] |
| - | [[Category: Influenza virus]] | + | [[Category: Pflug A]] |
| - | [[Category: Rna-dependent rna polymerase]] | + | |
| - | [[Category: Viral protein]] | + | |
