View source for 7nk2


==1918 H1N1 Viral influenza polymerase heterotrimer with Nb8202 core==
<StructureSection load='7nk2' size='340' side='right'caption='[[7nk2]], [[Resolution|resolution]] 4.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nk2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae_mixed_library Camelidae mixed library], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Brevig_Mission/1/1918(H1N1)) Influenza A virus (A/Brevig Mission/1/1918(H1N1))] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NK2 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]] 4.84&#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=7nk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nk2 OCA], [https://pdbe.org/7nk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nk2 RCSB], [https://www.ebi.ac.uk/pdbsum/7nk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nk2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RDRP_I18A0 RDRP_I18A0] 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.[HAMAP-Rule:MF_04065]
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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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==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Camelidae mixed library]]
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Carrique L]]
[[Category: Fodor E]]
[[Category: Grimes JM]]
[[Category: Keown JR]]