View source for 4mhh


==Crystal structure of Fab H5M9 in complex with influenza virus hemagglutinin from A/Viet Nam/1203/2004 (H5N1)==
<StructureSection load='4mhh' size='340' side='right'caption='[[4mhh]], [[Resolution|resolution]] 3.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mhh]] is a 12 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))] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MHH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=4mhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhh OCA], [https://pdbe.org/4mhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mhh RCSB], [https://www.ebi.ac.uk/pdbsum/4mhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I96A0 HEMA_I96A0] 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 ==
Despite substantial efforts to control and contain influenza H5N1 viruses, 'bird flu' viruses continue to spread and evolve. Neutralizing antibodies against conserved epitopes on the viral hemagglutinin (HA) could confer immunity to the diverse H5N1 influenza virus strains and provide information for effective vaccine design. Here, we report on characterization of a broadly neutralizing murine monoclonal antibody H5M9 to most H5N1 clades and sub-clades that was elicited by immunization with viral HA of A/goose/Guangdong/1/96 (H5N1), the immediate precursor of the current dominant strains of H5N1 viruses. Crystal structures of Fab' H5M9 with H5 HAs of A/Vietnam/1203/2004 and A/goose/Guangdong/1/96 reveal a conserved epitope in the HA1 vestigial esterase subdomain that is some distance from the receptor binding site, and partially overlaps antigenic site C of H3 HA. Further epitope characterization by selection of escape mutant and epitope mapping by flow cytometry analysis of site-directed mutagenesis of HA with yeast cell surface display identified four residues that are critical for H5M9 binding. D53, Y274, E83a and N276 are all conserved in H5N1 HAs and are not in H5 epitopes identified by other mouse or human antibodies. Antibody H5M9 is effective in protection of H5N1 virus both prophylactically and therapeutically and appears to neutralize by blocking both virus receptor binding and post-attachment steps. Thus, the H5M9 epitope identified here should provide valuable insights into H5N1 vaccine design and improvement, as well as antibody-based therapies for treatment of H5N1 infection.

A Unique and Conserved Neutralization Epitope in H5N1 Influenza Viruses Identified by a Murine Antibody against the A/goose/Guangdong/1/96 Hemagglutinin.,Zhu X, Guo YH, Jiang T, Wang YD, Chan KH, Li XF, Yu W, McBride R, Paulson JC, Yuen KY, Qin CF, Che XY, Wilson IA J Virol. 2013 Sep 18. PMID:24049169<ref>PMID:24049169</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Wilson IA]]
[[Category: Zhu X]]