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| | ==Crystal structure of Fab H7.167 in complex with influenza virus hemagglutinin from A/Shanghai/02/2013 (H7N9)== | | ==Crystal structure of Fab H7.167 in complex with influenza virus hemagglutinin from A/Shanghai/02/2013 (H7N9)== |
| - | <StructureSection load='5v2a' size='340' side='right' caption='[[5v2a]], [[Resolution|resolution]] 4.66Å' scene=''> | + | <StructureSection load='5v2a' size='340' side='right'caption='[[5v2a]], [[Resolution|resolution]] 4.66Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v2a]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5f45 5f45]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V2A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v2a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/chicken/Henan/109/2013(H7N9)) Influenza A virus (A/chicken/Henan/109/2013(H7N9))] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/pigeon/Wuxi/0405007G/2013(H7N9)) Influenza A virus (A/pigeon/Wuxi/0405007G/2013(H7N9))]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5f45 5f45]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V2A 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></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]] 4.656Å</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=5v2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v2a OCA], [http://pdbe.org/5v2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v2a RCSB], [http://www.ebi.ac.uk/pdbsum/5v2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v2a ProSAT]</span></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></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=5v2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v2a OCA], [https://pdbe.org/5v2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v2a RCSB], [https://www.ebi.ac.uk/pdbsum/5v2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v2a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0R5TXT5_9INFA A0A0R5TXT5_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:SAAS00046902] [[http://www.uniprot.org/uniprot/A0A097PHH8_9INFA A0A097PHH8_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:SAAS00046902] | + | [https://www.uniprot.org/uniprot/A0A0R5TXT5_9INFA A0A0R5TXT5_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:SAAS00046902] |
| | <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 5v2a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5v2a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Wilson, I A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Zhang, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhu, X]] | + | [[Category: Wilson IA]] |
| - | [[Category: Hemagglutinin]] | + | [[Category: Zhang H]] |
| - | [[Category: Human antibody]] | + | [[Category: Zhu X]] |
| - | [[Category: Receptor-binding site]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
A0A0R5TXT5_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:SAAS00046902]
Publication Abstract from PubMed
Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors. We isolated 12 naturally occurring mAbs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and HA-inhibiting activities. The 5 neutralizing mAbs exhibited narrow breadth of reactivity with influenza H7 strains. Epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mAbs bind near the receptor-binding pocket on HA. All 5 neutralizing mAbs possessed low numbers of somatic mutations, suggesting the clones arose from naive B cells. The most potent mAb, H7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mAb markedly reduced viral lung titers.
H7N9 influenza virus neutralizing antibodies that possess few somatic mutations.,Thornburg NJ, Zhang H, Bangaru S, Sapparapu G, Kose N, Lampley RM, Bombardi RG, Yu Y, Graham S, Branchizio A, Yoder SM, Rock MT, Creech CB, Edwards KM, Lee D, Li S, Wilson IA, Garcia-Sastre A, Albrecht RA, Crowe JE Jr J Clin Invest. 2016 Apr 1;126(4):1482-94. doi: 10.1172/JCI85317. Epub 2016 Mar 7. PMID:26950424[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Thornburg NJ, Zhang H, Bangaru S, Sapparapu G, Kose N, Lampley RM, Bombardi RG, Yu Y, Graham S, Branchizio A, Yoder SM, Rock MT, Creech CB, Edwards KM, Lee D, Li S, Wilson IA, Garcia-Sastre A, Albrecht RA, Crowe JE Jr. H7N9 influenza virus neutralizing antibodies that possess few somatic mutations. J Clin Invest. 2016 Apr 1;126(4):1482-94. doi: 10.1172/JCI85317. Epub 2016 Mar 7. PMID:26950424 doi:http://dx.doi.org/10.1172/JCI85317
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