View source for 6iut


==Crystal structure of influenza A virus H5 hemagglutinin globular head in complex with the Fab of antibody AVFluIgG01==
<StructureSection load='6iut' size='340' side='right'caption='[[6iut]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6iut]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Anhui/1/2005(H5N1)) Influenza A virus (A/Anhui/1/2005(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IUT 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=6iut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iut OCA], [https://pdbe.org/6iut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iut RCSB], [https://www.ebi.ac.uk/pdbsum/6iut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iut ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q1WDM0_9INFA Q1WDM0_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:SAAS013829_004_327643]
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== Publication Abstract from PubMed ==
Most neutralizing antibodies against highly pathogenic avian influenza A virus H5N1 recognize the receptor-binding site (RBS) on the globular head domain and the stem of H5N1 hemagglutinin (HA). Through comprehensive analysis of multiple human protective antibodies, we previously identified four vulnerable sites (VS1-VS4) on the globular head domain. Among them, the VS1, occupying the opposite side of the RBS on the same HA, was defined by the epitope of antibody 65C6. In this study, we report the crystal structures of two additional human H5N1 antibodies isolated from H5N1-infected individuals, 3C11 and AVFluIgG01, bound to the head at 2.33 and 2.30 A resolution, respectively. These two new antibody epitopes have large overlap with and extend beyond the original VS1. Site-directed mutagenesis experiments identified eight pivotal residues (Ser-126b, Lys-165, Arg-166, Ser-167, Tyr-168, Asn-169, Thr-171, and Asn-172) critical for 65C6, 3C11 and AVFluIgG01 binding and neutralization activities. These residues formed a unique "Y"-shape surface on H5N1 globular head and are highly conserved among H5N1 viruses. Our results further support the existence of a vulnerable site distinct from the RBS and the stem region of H5N1 HA, and future design of immunogens should take this particular site into consideration.

Structural and functional definition of a vulnerable site on the hemagglutinin of highly pathogenic avian influenza A virus H5N1.,Wang P, Zuo Y, Sun J, Zuo T, Zhang S, Guo S, Shi X, Liang M, Zhou P, Zhang L, Wang X J Biol Chem. 2019 Feb 8. pii: RA118.007008. doi: 10.1074/jbc.RA118.007008. PMID:30737282<ref>PMID:30737282</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 6iut" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sun J]]
[[Category: Wang P]]
[[Category: Wang X]]
[[Category: Zhang L]]
[[Category: Zuo Y]]