6wiz: Difference between revisions

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==Crystal structure of Fab 54-1G05 bound to H1 influenza hemagglutinin==
<StructureSection load='6wiz' size='340' side='right'caption='[[6wiz]]' scene=''>
<StructureSection load='6wiz' size='340' side='right'caption='[[6wiz]], [[Resolution|resolution]] 4.20&Aring;' 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 [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
<table><tr><td colspan='2'>[[6wiz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WIZ FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wiz OCA], [http://pdbe.org/6wiz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wiz RCSB], [http://www.ebi.ac.uk/pdbsum/6wiz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wiz ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.2&#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=6wiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wiz OCA], [https://pdbe.org/6wiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wiz RCSB], [https://www.ebi.ac.uk/pdbsum/6wiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wiz ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A7UPX0_9INFA A7UPX0_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.[RuleBase:RU003324][SAAS:SAAS00145386]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain VH6-1. We describe two genetically similar VH6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. One clonotype evolved from a germline precursor recognizing influenza group 1 subtypes to gain breadth to group 2 subtypes. The other clonotype recognized group 2 subtypes and developed binding to group 1 subtypes through somatic hypermutation. Crystal structures reveal that the specificity differences are primarily mediated by complementarity-determining region H3 (CDR H3). Thus, while VH6-1 provides a framework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions during VDJ recombination can alter reactivity and evolutionary pathways toward increased breadth.
Convergent Evolution in Breadth of Two VH6-1-Encoded Influenza Antibody Clonotypes from a Single Donor.,Wu NC, Andrews SF, Raab JE, O'Connell S, Schramm CA, Ding X, Chambers MJ, Leung K, Wang L, Zhang Y, Mascola JR, Douek DC, Ledgerwood JE, McDermott AB, Wilson IA Cell Host Microbe. 2020 Sep 9;28(3):434-444.e4. doi: 10.1016/j.chom.2020.06.003. , Epub 2020 Jul 2. PMID:32619441<ref>PMID:32619441</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wiz" style="background-color:#fffaf0;"></div>
==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Influenza A virus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Z-disk]]
[[Category: Wilson IA]]
[[Category: Wu NC]]

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