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==1918 H1N1 Viral influenza polymerase heterotrimer - Endonuclease and priming loop ordered (Class2a)==
<StructureSection load='7nha' size='340' side='right'caption='[[7nha]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nha]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Brevig_Mission/1/1918(H1N1)) Influenza A virus (A/Brevig Mission/1/1918(H1N1))], [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] 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=7NHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NHA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.91&#8491;</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=7nha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nha OCA], [https://pdbe.org/7nha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nha RCSB], [https://www.ebi.ac.uk/pdbsum/7nha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nha ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PA_I18A0 PA_I18A0] Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063]
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== Publication Abstract from PubMed ==
Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.

Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.,Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM Nat Commun. 2022 Jan 11;13(1):251. doi: 10.1038/s41467-021-27950-w. PMID:35017564<ref>PMID:35017564</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7nha" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Synthetic construct]]
[[Category: Carrique L]]
[[Category: Fodor E]]
[[Category: Grimes JM]]
[[Category: Keown JR]]