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| | <StructureSection load='5m3j' size='340' side='right'caption='[[5m3j]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='5m3j' size='340' side='right'caption='[[5m3j]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5m3j]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus_(b/memphis/13/03) Influenza b virus (b/memphis/13/03)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M3J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5M3J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5m3j]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus] and [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Memphis/13/2003) Influenza B virus (B/Memphis/13/2003)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M3J FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</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=1601067 Influenza B virus (B/Memphis/13/03)]), PB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1601067 Influenza B virus (B/Memphis/13/03)]), PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1601067 Influenza B virus (B/Memphis/13/03)])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=5m3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m3j OCA], [https://pdbe.org/5m3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m3j RCSB], [https://www.ebi.ac.uk/pdbsum/5m3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m3j ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5m3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m3j OCA], [http://pdbe.org/5m3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m3j RCSB], [http://www.ebi.ac.uk/pdbsum/5m3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m3j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q5V8Z9_9INFB Q5V8Z9_9INFB] |
| | <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: Homo sapiens]] |
| | + | [[Category: Influenza B virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA-directed RNA polymerase]]
| + | [[Category: Cusack S]] |
| - | [[Category: Cusack, S]] | + | [[Category: Lukarska M]] |
| - | [[Category: Lukarska, M]] | + | [[Category: Pflug A]] |
| - | [[Category: Pflug, A]] | + | |
| - | [[Category: Influenza b virus rna-dependent rna polymerase]]
| + | |
| - | [[Category: Pol ii serine 5 phosphorylated ctd peptide]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Vrna promoter]]
| + | |
| Structural highlights
Function
Q5V8Z9_9INFB
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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