View source for 6bks


==Crystal structure of the A/Wyoming/3/2003 (H3N2) influenza virus hemagglutinin D190E mutant in complex with 6'-SLN==
<StructureSection load='6bks' size='340' side='right'caption='[[6bks]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bks]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Nymc_X-149C6(Puerto_Rico/8/1934-Wyoming/03/2003)(H3N2)) Influenza A virus (A/Nymc X-149C6(Puerto Rico/8/1934-Wyoming/03/2003)(H3N2))] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Wyoming/3e/2003(H3)) Influenza A virus (A/Wyoming/3e/2003(H3))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BKS 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=6bks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bks OCA], [https://pdbe.org/6bks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bks RCSB], [https://www.ebi.ac.uk/pdbsum/6bks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bks ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4GYF9_9INFA A4GYF9_9INFA] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[SAAS:SAAS00842802]  Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[RuleBase:RU003324]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses is critical for attachment to host cells, which imposes a functional constraint on its natural evolution. On the other hand, being part of the major antigenic sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the immune system. From large-scale mutagenesis experiments, we here show that several of the natural RBS substitutions become integrated into an extensive epistatic network that prevents substitution reversion. X-ray structural analysis reveals the mechanistic consequences as well as changes in the mode of receptor binding. Further studies are necessary to elucidate whether such entrenchment limits future options for immune escape or adversely affect long-term viral fitness.

A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site.,Wu NC, Thompson AJ, Xie J, Lin CW, Nycholat CM, Zhu X, Lerner RA, Paulson JC, Wilson IA Nat Commun. 2018 Mar 28;9(1):1264. doi: 10.1038/s41467-018-03663-5. PMID:29593268<ref>PMID:29593268</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6bks" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Wilson IA]]
[[Category: Wu NC]]