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| | <StructureSection load='6ocb' size='340' side='right'caption='[[6ocb]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6ocb' size='340' side='right'caption='[[6ocb]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ocb]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/I68a4 I68a4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OCB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OCB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ocb]] 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/Hong_Kong/1/1968(H3N2)) Influenza A virus (A/Hong Kong/1/1968(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OCB FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=506350 I68A4])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6ocb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ocb OCA], [http://pdbe.org/6ocb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ocb RCSB], [http://www.ebi.ac.uk/pdbsum/6ocb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ocb ProSAT]</span></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=6ocb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ocb OCA], [https://pdbe.org/6ocb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ocb RCSB], [https://www.ebi.ac.uk/pdbsum/6ocb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ocb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] | | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: I68a4]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lang, S]] | + | [[Category: Lang S]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Wilson IA]] |
| - | [[Category: Anti-flu antibody]]
| + | |
| - | [[Category: Ha head domain]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.
A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.,Bangaru S, Lang S, Schotsaert M, Vanderven HA, Zhu X, Kose N, Bombardi R, Finn JA, Kent SJ, Gilchuk P, Gilchuk I, Turner HL, Garcia-Sastre A, Li S, Ward AB, Wilson IA, Crowe JE Jr Cell. 2019 May 16;177(5):1136-1152.e18. doi: 10.1016/j.cell.2019.04.011. PMID:31100268[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bangaru S, Lang S, Schotsaert M, Vanderven HA, Zhu X, Kose N, Bombardi R, Finn JA, Kent SJ, Gilchuk P, Gilchuk I, Turner HL, Garcia-Sastre A, Li S, Ward AB, Wilson IA, Crowe JE Jr. A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface. Cell. 2019 May 16;177(5):1136-1152.e18. doi: 10.1016/j.cell.2019.04.011. PMID:31100268 doi:http://dx.doi.org/10.1016/j.cell.2019.04.011
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