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| <StructureSection load='3cm8' size='340' side='right'caption='[[3cm8]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='3cm8' size='340' side='right'caption='[[3cm8]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3cm8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9infa 9infa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CM8 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3cm8]] is a 2 chain structure with sequence from [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=3CM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CM8 FirstGlance]. <br> |
| </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></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]] 2.899Å</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=3cm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cm8 OCA], [https://pdbe.org/3cm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cm8 RCSB], [https://www.ebi.ac.uk/pdbsum/3cm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cm8 ProSAT]</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=3cm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cm8 OCA], [https://pdbe.org/3cm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cm8 RCSB], [https://www.ebi.ac.uk/pdbsum/3cm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cm8 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/RDRP_I97A1 RDRP_I97A1]] RNA-dependent RNA polymerase which is responsible for replication and transcription of virus RNA segments. The transcription of viral mRNAs occurs by a unique mechanism called cap-snatching. 5' methylated caps of cellular mRNAs are cleaved after 10-13 nucleotides by PA. In turn, these short capped RNAs are used as primers by PB1 for transcription of viral mRNAs. During virus replication, PB1 initiates RNA synthesis and copy vRNA into complementary RNA (cRNA) which in turn serves as a template for the production of more vRNAs.[UniProtKB:P03431]
| | [https://www.uniprot.org/uniprot/Q9EA60_9INFA Q9EA60_9INFA] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The recent emergence of highly pathogenic avian influenza A virus strains with subtype H5N1 pose a global threat to human health. Elucidation of the underlying mechanisms of viral replication is critical for development of anti-influenza virus drugs. The influenza RNA-dependent RNA polymerase (RdRp) heterotrimer has crucial roles in viral RNA replication and transcription. It contains three proteins: PA, PB1 and PB2. PB1 harbours polymerase and endonuclease activities and PB2 is responsible for cap binding; PA is implicated in RNA replication and proteolytic activity, although its function is less clearly defined. Here we report the 2.9 angstrom structure of avian H5N1 influenza A virus PA (PA(C), residues 257-716) in complex with the PA-binding region of PB1 (PB1(N), residues 1-25). PA(C) has a fold resembling a dragon's head with PB1(N) clamped into its open 'jaws'. PB1(N) is a known inhibitor that blocks assembly of the polymerase heterotrimer and abolishes viral replication. Our structure provides details for the binding of PB1(N) to PA(C) at the atomic level, demonstrating a potential target for novel anti-influenza therapeutics. We also discuss a potential nucleotide binding site and the roles of some known residues involved in polymerase activity. Furthermore, to explore the role of PA in viral replication and transcription, we propose a model for the influenza RdRp heterotrimer by comparing PA(C) with the lambda3 reovirus polymerase structure, and docking the PA(C) structure into an available low resolution electron microscopy map.
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| Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus.,He X, Zhou J, Bartlam M, Zhang R, Ma J, Lou Z, Li X, Li J, Joachimiak A, Zeng Z, Ge R, Rao Z, Liu Y Nature. 2008 Aug 28;454(7208):1123-6. Epub 2008 Jul 9. PMID:18615018<ref>PMID:18615018</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 3cm8" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| | [[Category: Influenza A virus]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: RNA-directed RNA polymerase]]
| | [[Category: He X]] |
| [[Category: He, X]] | | [[Category: Liu Y]] |
| [[Category: Liu, Y]] | | [[Category: Ma J]] |
| [[Category: Ma, J]] | | [[Category: Rao Z]] |
| [[Category: Rao, Z]] | | [[Category: Zeng Z]] |
| [[Category: Zeng, Z]] | | [[Category: Zhang R]] |
| [[Category: Zhang, R]] | | [[Category: Zhou J]] |
| [[Category: Zhou, J]] | |
| [[Category: Nucleotide-binding]]
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| [[Category: Nucleotidyltransferase]]
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| [[Category: Protein-peptide complex]]
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| [[Category: Rna binding protein-transferase complex]]
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| [[Category: Rna replication]]
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| [[Category: Rna-directed rna polymerase]]
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| [[Category: Transferase]]
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