View source for 4kdn


==Crystal structure of the hemagglutinin of ferret-transmissible H5N1 virus in complex with avian receptor analog LSTa==
<StructureSection load='4kdn' size='340' side='right'caption='[[4kdn]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kdn]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KDN 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]] 2.483&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4kdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kdn OCA], [https://pdbe.org/4kdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kdn RCSB], [https://www.ebi.ac.uk/pdbsum/4kdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kdn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6DQ33_I04A1 Q6DQ33_I04A1] 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]
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== Publication Abstract from PubMed ==
Avian influenza A virus continues to pose a global threat with occasional H5N1 human infections, which is emphasized by a recent severe human infection caused by avian-origin H7N9 in China. Luckily these viruses do not transmit efficiently in human populations. With a few amino acid substitutions of the hemagglutinin H5 protein in the laboratory, two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model. Here in this study one of the mutant H5 proteins developed by Kawaoka's group (VN1203mut) was expressed in a baculovirus system and its receptor-binding properties were assessed. We herein show that the VN1203mut had a dramatically reduced binding affinity for the avian alpha2,3-linkage receptor compared to wild type but showed no detectable increase in affinity for the human alpha2,6-linkage receptor, using Surface Plasmon Resonance techonology. Further, the crystal structures of the VN1203mut and its complexes with either human or avian receptors demonstrate that the VN1203mut binds the human receptor in the same binding manner (cis conformation) as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses. Our receptor binding and crystallographic data shown here further confirm that the ability to bind the avian receptor has to decrease for a higher human receptor binding affinity. As the Q226L substitution is shown important for obtaining human receptor binding, we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.

Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut).,Lu X, Shi Y, Zhang W, Zhang Y, Qi J, Gao GF Protein Cell. 2013 Jun 20. PMID:23794001<ref>PMID:23794001</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4kdn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Gao GF]]
[[Category: Lu X]]
[[Category: Qi J]]
[[Category: Shi Y]]
[[Category: Zhang W]]
[[Category: Zhang Y]]