View source for 5vtr


==Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin G225L/L226S mutant in complex with 6'-SLN==
<StructureSection load='5vtr' size='340' side='right'caption='[[5vtr]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vtr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Hong_Kong/1/1968(H3N2)) Influenza A virus (A/Hong Kong/1/1968(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VTR 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]] 2.5&#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=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900046:6-sialyl-N-acetyllactosamine'>PRD_900046</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=5vtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vtr OCA], [https://pdbe.org/5vtr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vtr RCSB], [https://www.ebi.ac.uk/pdbsum/5vtr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vtr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I68A4 HEMA_I68A4] 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 (By similarity).
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== Publication Abstract from PubMed ==
Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody. This functional sequence diversity is made possible by pervasive epistasis in the RBS 220-loop and can be buffered by avidity in viral receptor binding. Overall, our study reveals that the HA RBS can accommodate a much greater range of sequence diversity than previously thought, which has significant implications for the complex evolutionary interrelationships between receptor specificity and immune escape.

Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin.,Wu NC, Xie J, Zheng T, Nycholat CM, Grande G, Paulson JC, Lerner RA, Wilson IA Cell Host Microbe. 2017 Jun 14;21(6):742-753.e8. doi: 10.1016/j.chom.2017.05.011. PMID:28618270<ref>PMID:28618270</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 5vtr" style="background-color:#fffaf0;"></div>

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