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==== | ==Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer== | ||
<StructureSection load='6wxl' size='340' side='right'caption='[[6wxl]]' scene=''> | <StructureSection load='6wxl' size='340' side='right'caption='[[6wxl]], [[Resolution|resolution]] 2.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[6wxl]] 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/Shanghai/JS01/2013(H7N9)) Influenza A virus (A/Shanghai/JS01/2013(H7N9))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WXL FirstGlance]. <br> | ||
</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=6wxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxl OCA], [https://pdbe.org/6wxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wxl RCSB], [https://www.ebi.ac.uk/pdbsum/6wxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxl ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.76Å</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=6wxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxl OCA], [https://pdbe.org/6wxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wxl RCSB], [https://www.ebi.ac.uk/pdbsum/6wxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxl ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A067Y6L0_9INFA A0A067Y6L0_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 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] 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.[RuleBase:RU003324] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite. | |||
Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.,Cheung CS, Gorman J, Andrews SF, Rawi R, Reveiz M, Shen CH, Wang Y, Harris DR, Nazzari AF, Olia AS, Raab J, Teng IT, Verardi R, Wang S, Yang Y, Chuang GY, McDermott AB, Zhou T, Kwong PD Structure. 2022 Jul 7;30(7):993-1003.e6. doi: 10.1016/j.str.2022.04.003. Epub , 2022 Apr 29. PMID:35489332<ref>PMID:35489332</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6wxl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gorman J]] | ||
[[Category: Kwong PD]] | |||