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| | ==Crystal structure of H6 hemagglutinin G225D mutant from Taiwan (2013) H6N1 influenza virus== | | ==Crystal structure of H6 hemagglutinin G225D mutant from Taiwan (2013) H6N1 influenza virus== |
| - | <StructureSection load='5t08' size='340' side='right' caption='[[5t08]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='5t08' size='340' side='right'caption='[[5t08]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t08]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/H6n1_subtype H6n1 subtype]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T08 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t08]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/H6N1_subtype H6N1 subtype]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T08 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.1895Å</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=119212 H6N1 subtype])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t08 OCA], [http://pdbe.org/5t08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t08 RCSB], [http://www.ebi.ac.uk/pdbsum/5t08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t08 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=5t08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t08 OCA], [https://pdbe.org/5t08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t08 RCSB], [https://www.ebi.ac.uk/pdbsum/5t08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t08 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0J9X268_9INFA A0A0J9X268_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.[SAAS:SAAS00842036] 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] [[http://www.uniprot.org/uniprot/A0A0J9X267_9INFA A0A0J9X267_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] | + | [https://www.uniprot.org/uniprot/A0A0J9X268_9INFA A0A0J9X268_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.[SAAS:SAAS00842036] 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5t08" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5t08" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: H6n1 subtype]] | + | [[Category: H6N1 subtype]] |
| - | [[Category: Tzarum, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Tzarum N]] |
| - | [[Category: Zhu, X]] | + | [[Category: Wilson IA]] |
| - | [[Category: Ha]] | + | [[Category: Zhu X]] |
| - | [[Category: Hemagglutinin]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Influenza virus]]
| + | |
| - | [[Category: Receptor specificity]]
| + | |
| Structural highlights
Function
A0A0J9X268_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.[SAAS:SAAS00842036] 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]
Publication Abstract from PubMed
In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcalpha2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcalpha2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.
A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors.,de Vries RP, Tzarum N, Peng W, Thompson AJ, Ambepitiya Wickramasinghe IN, de la Pena ATT, van Breemen MJ, Bouwman KM, Zhu X, McBride R, Yu W, Sanders RW, Verheije MH, Wilson IA, Paulson JC EMBO Mol Med. 2017 Sep;9(9):1314-1325. doi: 10.15252/emmm.201707726. PMID:28694323[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ de Vries RP, Tzarum N, Peng W, Thompson AJ, Ambepitiya Wickramasinghe IN, de la Pena ATT, van Breemen MJ, Bouwman KM, Zhu X, McBride R, Yu W, Sanders RW, Verheije MH, Wilson IA, Paulson JC. A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Mol Med. 2017 Sep;9(9):1314-1325. doi: 10.15252/emmm.201707726. PMID:28694323 doi:http://dx.doi.org/10.15252/emmm.201707726
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