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| | <StructureSection load='4kvn' size='340' side='right'caption='[[4kvn]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='4kvn' size='340' side='right'caption='[[4kvn]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kvn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/perth/16/2009(h3n2)) Influenza a virus (a/perth/16/2009(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KVN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KVN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kvn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Perth/16/2009(H3N2)) Influenza A virus (A/Perth/16/2009(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KVN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </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>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA, Hemagglutinin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=654811 Influenza A virus (A/Perth/16/2009(H3N2))])</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=4kvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kvn OCA], [https://pdbe.org/4kvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kvn RCSB], [https://www.ebi.ac.uk/pdbsum/4kvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kvn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kvn OCA], [http://pdbe.org/4kvn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kvn RCSB], [http://www.ebi.ac.uk/pdbsum/4kvn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kvn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/C6KNH7_9INFA C6KNH7_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:SAAS001364_004_327643] | + | [https://www.uniprot.org/uniprot/C6KNH7_9INFA C6KNH7_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:SAAS001364_004_327643] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fong, R]] | + | [[Category: Fong R]] |
| - | [[Category: Lupardus, P J]] | + | [[Category: Lupardus PJ]] |
| - | [[Category: Swem, L R]] | + | [[Category: Swem LR]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Igg]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
C6KNH7_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:SAAS001364_004_327643]
Publication Abstract from PubMed
Recent advances enabling the cloning of human immunoglobulin G genes have proven effective for discovering monoclonal antibodies with therapeutic potential. However, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting plasma cells or plasmablasts. We describe an in vivo enrichment technique that identifies broadly neutralizing human antibodies with high frequency. For this technique, human peripheral blood mononuclear cells from vaccinated donors are activated and enriched in an antigen-specific manner for the production of numerous antigen-specific plasmablasts. Using this technology, we identified four broadly neutralizing influenza A antibodies by screening only 840 human antibodies. Two of these antibodies neutralize every influenza A human isolate tested and perform better than the current anti-influenza A therapeutic, oseltamivir, in treating severe influenza infection in mice and ferrets. Furthermore, these antibodies elicit robust in vivo synergism when combined with oseltamivir, thus highlighting treatment strategies that could benefit influenza-infected patients.
An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies.,Nakamura G, Chai N, Park S, Chiang N, Lin Z, Chiu H, Fong R, Yan D, Kim J, Zhang J, Lee WP, Estevez A, Coons M, Xu M, Lupardus P, Balazs M, Swem LR Cell Host Microbe. 2013 Jul 17;14(1):93-103. doi: 10.1016/j.chom.2013.06.004. PMID:23870317[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakamura G, Chai N, Park S, Chiang N, Lin Z, Chiu H, Fong R, Yan D, Kim J, Zhang J, Lee WP, Estevez A, Coons M, Xu M, Lupardus P, Balazs M, Swem LR. An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies. Cell Host Microbe. 2013 Jul 17;14(1):93-103. doi: 10.1016/j.chom.2013.06.004. PMID:23870317 doi:10.1016/j.chom.2013.06.004
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