View source for 7z42


==Influenza B polymerase with Pol II pSer5 CTD peptide mimic bound in site 2B==
<StructureSection load='7z42' size='340' side='right'caption='[[7z42]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7z42]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z42 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.418&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7z42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z42 OCA], [https://pdbe.org/7z42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z42 RCSB], [https://www.ebi.ac.uk/pdbsum/7z42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z42 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5V8Z9_9INFB Q5V8Z9_9INFB] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
During annual influenza epidemics, influenza B viruses (IBVs) co-circulate with influenza A viruses (IAVs), can become predominant and cause severe morbidity and mortality. Phylogenetic analyses suggest that IAVs (primarily avian viruses) and IBVs (primarily human viruses) have diverged over long time scales. Identifying their common and distinctive features is an effective approach to increase knowledge about the molecular details of influenza infection. The virus-encoded RNA-dependent RNA polymerases (FluPolB and FluPolA) are PB1-PB2-PA heterotrimers that perform transcription and replication of the viral genome in the nucleus of infected cells. Initiation of viral mRNA synthesis requires a direct association of FluPol with the host RNA polymerase II (RNAP II), in particular the repetitive C-terminal domain (CTD) of the major RNAP II subunit, to enable "cap-snatching" whereby 5'-capped oligomers derived from nascent RNAP II transcripts are pirated to prime viral transcription. Here, we present the first high-resolution co-crystal structure of FluPolB bound to a CTD mimicking peptide at a binding site crossing from PA to PB2. By performing structure-based mutagenesis of FluPolB and FluPolA followed by a systematic investigation of FluPol-CTD binding, FluPol activity and viral phenotype, we demonstrate that IBVs and IAVs have evolved distinct binding interfaces to recruit the RNAP II CTD, despite the CTD sequence being highly conserved across host species. We find that the PB2 627 subdomain, a major determinant of FluPol-host cell interactions and IAV host-range, is involved in CTD-binding for IBVs but not for IAVs, and we show that FluPolB and FluPolA bind to the host RNAP II independently of the CTD. Altogether, our results suggest that the CTD-binding modes of IAV and IBV may represent avian- and human-optimized binding modes, respectively, and that their divergent evolution was shaped by the broader interaction network between the FluPol and the host transcriptional machinery.

Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD.,Krischuns T, Isel C, Drncova P, Lukarska M, Pflug A, Paisant S, Navratil V, Cusack S, Naffakh N PLoS Pathog. 2022 May 23;18(5):e1010328. doi: 10.1371/journal.ppat.1010328. , eCollection 2022 May. PMID:35605026<ref>PMID:35605026</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7z42" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Influenza B virus]]
[[Category: Large Structures]]
[[Category: Cusack S]]
[[Category: Drncova P]]