View source for 7scn


==Structure of H1 NC99 influenza hemagglutinin bound to Fab 310-63E6==
<StructureSection load='7scn' size='340' side='right'caption='[[7scn]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7scn]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/South_Canterbury/35/2000(H1N1)) Influenza A virus (A/South Canterbury/35/2000(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SCN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.02&#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=7scn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7scn OCA], [https://pdbe.org/7scn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7scn RCSB], [https://www.ebi.ac.uk/pdbsum/7scn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7scn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I00A1 HEMA_I00A1] 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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072]
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== Publication Abstract from PubMed ==
Human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin stalk of group 1 influenza A viruses (IAVs) are biased for IGHV1-69 alleles that use phenylalanine (F54) but not leucine (L54) within their CDRH2 loops. Despite this, we demonstrated that both alleles encode for human IAV bnAbs that employ structurally convergent modes of contact to the same epitope. To resolve differences in lineage expandability, we compared F54 versus L54 as substrate within humanized mice, where antibodies develop with human-like CDRH3 diversity but are restricted to single V(H) genes. While both alleles encoded for bnAb precursors, only F54 IGHV1-69 supported elicitation of heterosubtypic serum bnAbs following immunization with a stalk-only nanoparticle vaccine. L54 IGHV1-69 was unproductive, co-encoding for anergic B cells and autoreactive stalk antibodies that were cleared from B cell memory. Moreover, human stalk antibodies also demonstrated L54-dependent autoreactivity. Therefore, IGHV1-69 polymorphism, which is skewed ethnically, gates tolerance and vaccine expandability of influenza bnAbs.

Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus.,Sangesland M, Torrents de la Pena A, Boyoglu-Barnum S, Ronsard L, Mohamed FAN, Moreno TB, Barnes RM, Rohrer D, Lonberg N, Ghebremichael M, Kanekiyo M, Ward A, Lingwood D Immunity. 2022 Sep 13;55(9):1693-1709.e8. doi: 10.1016/j.immuni.2022.07.006. Epub , 2022 Aug 10. PMID:35952670<ref>PMID:35952670</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 7scn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Torrents de la Pena A]]
[[Category: Ward A]]