View source for 5jw4


==Structure of MEDI8852 Fab Fragment in Complex with H5 HA==
<StructureSection load='5jw4' size='340' side='right'caption='[[5jw4]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jw4]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=5JW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JW4 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]] 3.7&#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></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=5jw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jw4 OCA], [https://pdbe.org/5jw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jw4 RCSB], [https://www.ebi.ac.uk/pdbsum/5jw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jw4 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 ==
Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.

Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.,Kallewaard NL, Corti D, Collins PJ, Neu U, McAuliffe JM, Benjamin E, Wachter-Rosati L, Palmer-Hill FJ, Yuan AQ, Walker PA, Vorlaender MK, Bianchi S, Guarino B, De Marco A, Vanzetta F, Agatic G, Foglierini M, Pinna D, Fernandez-Rodriguez B, Fruehwirth A, Silacci C, Ogrodowicz RW, Martin SR, Sallusto F, Suzich JA, Lanzavecchia A, Zhu Q, Gamblin SJ, Skehel JJ Cell. 2016 Jul 28;166(3):596-608. doi: 10.1016/j.cell.2016.05.073. Epub 2016 Jul , 21. PMID:27453466<ref>PMID:27453466</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jw4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Collins PJ]]
[[Category: Gamblin SJ]]
[[Category: Martin SR]]
[[Category: Neu U]]
[[Category: Ogrodowicz RW]]
[[Category: Skehel JJ]]
[[Category: Vorlaender MK]]
[[Category: Walker PA]]