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| | ==Bat influenza A/H17N10 polymerase bound to four heptad repeats of serine 5 phosphorylated Pol II CTD== | | ==Bat influenza A/H17N10 polymerase bound to four heptad repeats of serine 5 phosphorylated Pol II CTD== |
| - | <StructureSection load='5m3h' size='340' side='right' caption='[[5m3h]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='5m3h' size='340' side='right'caption='[[5m3h]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5m3h]] is a 7 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=5M3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M3H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5m3h]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M3H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5m3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m3h OCA], [https://pdbe.org/5m3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m3h RCSB], [https://www.ebi.ac.uk/pdbsum/5m3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m3h ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m3h OCA], [http://pdbe.org/5m3h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m3h RCSB], [http://www.ebi.ac.uk/pdbsum/5m3h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m3h ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/H6QM92_9INFA H6QM92_9INFA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5m3h" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5m3h" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: RNA-directed RNA polymerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cusack, S]] | + | [[Category: Influenza A virus]] |
| - | [[Category: Lukarska, M]]
| + | [[Category: Large Structures]] |
| - | [[Category: Pflug, A]]
| + | [[Category: Cusack S]] |
| - | [[Category: Influenza rna-dependent rna polymerase]] | + | [[Category: Lukarska M]] |
| - | [[Category: Pol ii serine 5 phosphorylated ctd peptide]] | + | [[Category: Pflug A]] |
| - | [[Category: Transferase]] | + | |
| - | [[Category: Vrna promoter]] | + | |
| Structural highlights
Function
H6QM92_9INFA
Publication Abstract from PubMed
The heterotrimeric influenza polymerase (FluPol), comprising subunits PA, PB1 and PB2, binds to the conserved 5' and 3' termini (the 'promoter') of each of the eight single-stranded viral RNA (vRNA) genome segments and performs both transcription and replication of vRNA in the infected cell nucleus. To transcribe viral mRNAs, FluPol associates with cellular RNA polymerase II (Pol II), which enables it to take 5'-capped primers from nascent Pol II transcripts. Here we present a co-crystal structure of bat influenza A polymerase bound to a Pol II C-terminal domain (CTD) peptide mimic, which shows two distinct phosphoserine-5 (SeP5)-binding sites in the polymerase PA subunit, accommodating four CTD heptad repeats overall. Mutagenesis of the SeP5-contacting basic residues (PA K289, R454, K635 and R638) weakens CTD repeat binding in vitro without affecting the intrinsic cap-primed (transcription) or unprimed (replication) RNA synthesis activity of recombinant polymerase, whereas in cell-based minigenome assays the same mutations substantially reduce overall polymerase activity. Only recombinant viruses with a single mutation in one of the SeP5-binding sites can be rescued, but these viruses are severely attenuated and genetically unstable. Several previously described mutants that modulate virulence can be rationalized by our results, including a second site mutation (PA(C453R)) that enables the highly attenuated mutant virus (PA(R638A)) to revert to near wild-type infectivity. We conclude that direct binding of FluPol to the SeP5 Pol II CTD is fine-tuned to allow efficient viral transcription and propose that the CTD-binding site on FluPol could be targeted for antiviral drug development.
Structural basis of an essential interaction between influenza polymerase and Pol II CTD.,Lukarska M, Fournier G, Pflug A, Resa-Infante P, Reich S, Naffakh N, Cusack S Nature. 2017 Jan 5;541(7635):117-121. doi: 10.1038/nature20594. Epub 2016 Dec 21. PMID:28002402[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lukarska M, Fournier G, Pflug A, Resa-Infante P, Reich S, Naffakh N, Cusack S. Structural basis of an essential interaction between influenza polymerase and Pol II CTD. Nature. 2017 Jan 5;541(7635):117-121. doi: 10.1038/nature20594. Epub 2016 Dec 21. PMID:28002402 doi:http://dx.doi.org/10.1038/nature20594
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