View source for 4cqs


==H5 (VN1194) Asn186Lys Mutant Haemagglutinin in Complex with Avian Receptor Analogue 3'SLN==
<StructureSection load='4cqs' size='340' side='right'caption='[[4cqs]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cqs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Vietnam/1194/2004(H5N1)) Influenza A virus (A/Vietnam/1194/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CQS 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]] 2.55&#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=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4cqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqs OCA], [https://pdbe.org/4cqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cqs RCSB], [https://www.ebi.ac.uk/pdbsum/4cqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cqs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6DQ34_9INFA Q6DQ34_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 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).[RuleBase:RU003324][SAAS:SAAS008980_004_327643]
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== Publication Abstract from PubMed ==
Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Delta133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry.

Enhanced human receptor binding by H5 haemagglutinins.,Xiong X, Xiao H, Martin SR, Coombs PJ, Liu J, Collins PJ, Vachieri SG, Walker PA, Lin YP, McCauley JW, Gamblin SJ, Skehel JJ Virology. 2014 May;456-457:179-87. doi: 10.1016/j.virol.2014.03.008. Epub 2014, Apr 12. PMID:24889237<ref>PMID:24889237</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 4cqs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Collins PJ]]
[[Category: Coombs PJ]]
[[Category: Gamblin SJ]]
[[Category: Lin YP]]
[[Category: Liu J]]
[[Category: Martin SR]]
[[Category: McCauley JW]]
[[Category: Skehel JJ]]
[[Category: Vachieri SG]]
[[Category: Walker PA]]
[[Category: Xiao H]]
[[Category: Xiong X]]