View source for 4juj


==Crystal structure of 1918 pandemic influenza virus hemagglutinin mutant D225G complexed with human receptor analogue LSTc==
<StructureSection load='4juj' size='340' side='right'caption='[[4juj]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4juj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/South_Carolina/1/1918(H1N1)) Influenza A virus (A/South Carolina/1/1918(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JUJ 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]] 3.013&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</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=4juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4juj OCA], [https://pdbe.org/4juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4juj RCSB], [https://www.ebi.ac.uk/pdbsum/4juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4juj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I18A0 HEMA_I18A0] 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 uses sialic acids as cell entry receptors, and there are two main receptor forms, alpha2,6 linkage or alpha2,3 linkage to galactose, that determine virus host ranges (mammalian or avian). The receptor binding hemagglutinins (HAs) of both 1918 and 2009 pandemic H1N1 (18H1 and 09H1, respectively) influenza A viruses preferentially bind to the human alpha2,6 linkage receptor. A single D225G mutation in both H1s switches receptor binding specificity from alpha2,6 linkage binding to dual receptor binding. However, the molecular basis for this specificity switch is not fully understood. Here, we show via H1-ligand complex structures that the D225G substitution results in a loss of a salt bridge between amino acids D225 and K222, enabling the key residue Q226 to interact with the avian receptor, thereby obtaining dual receptor binding. This is further confirmed by a D225E mutant that retains human receptor binding specificity with the salt bridge intact.

Molecular Basis of the Receptor Binding Specificity Switch of the Hemagglutinins from both the 1918 and 2009 Pandemic Influenza A Viruses by a D225G Substitution.,Zhang W, Shi Y, Qi J, Gao F, Li Q, Fan Z, Yan J, Gao GF J Virol. 2013 May;87(10):5949-58. doi: 10.1128/JVI.00545-13. Epub 2013 Mar 20. PMID:23514882<ref>PMID:23514882</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 4juj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Fan Z]]
[[Category: Gao F]]
[[Category: Gao GF]]
[[Category: Li Q]]
[[Category: Qi J]]
[[Category: Shi Y]]
[[Category: Yan J]]
[[Category: Zhang W]]