View source for 5kuy


==Influenza hemagglutinin H3 A/Hong Kong/1/1968 in complex with designed inhibitor protein HSB.2A==
<StructureSection load='5kuy' size='340' side='right'caption='[[5kuy]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kuy]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Hong_Kong/1/1968(H3N2)) Influenza A virus (A/Hong Kong/1/1968(H3N2))] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KUY 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]] 2.598&#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=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=5kuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kuy OCA], [https://pdbe.org/5kuy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kuy RCSB], [https://www.ebi.ac.uk/pdbsum/5kuy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kuy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I68A4 HEMA_I68A4] 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 ==
Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site.,Strauch EM, Bernard SM, La D, Bohn AJ, Lee PS, Anderson CE, Nieusma T, Holstein CA, Garcia NK, Hooper KA, Ravichandran R, Nelson JW, Sheffler W, Bloom JD, Lee KK, Ward AB, Yager P, Fuller DH, Wilson IA, Baker D Nat Biotechnol. 2017 Jul;35(7):667-671. doi: 10.1038/nbt.3907. Epub 2017 Jun 12. PMID:28604661<ref>PMID:28604661</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 5kuy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bernard SM]]
[[Category: Wilson IA]]