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| | ==Crystal structure of influenza hemagglutinin (H5) in complex with a broadly neutralizing antibody F10== | | ==Crystal structure of influenza hemagglutinin (H5) in complex with a broadly neutralizing antibody F10== |
| - | <StructureSection load='3fku' size='340' side='right' caption='[[3fku]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='3fku' size='340' side='right'caption='[[3fku]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fku]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/viet_nam/1203/2004(h5n1)) Influenza a virus (a/viet nam/1203/2004(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fku]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FKU 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]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ibx|2ibx]], [[2fk0|2fk0]], [[2ghw|2ghw]]</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='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=284218 Influenza A virus (A/Viet Nam/1203/2004(H5N1))])</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=3fku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fku OCA], [https://pdbe.org/3fku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fku RCSB], [https://www.ebi.ac.uk/pdbsum/3fku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fku 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=3fku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fku OCA], [http://pdbe.org/3fku PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fku RCSB], [http://www.ebi.ac.uk/pdbsum/3fku PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fku ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q6DQ33_9INFA Q6DQ33_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:SAAS013829_004_327643] [[http://www.uniprot.org/uniprot/HEMA_I05A1 HEMA_I05A1]] 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. | + | [https://www.uniprot.org/uniprot/HEMA_I03A0 HEMA_I03A0] 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.[HAMAP-Rule:MF_04072] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fk/3fku_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fk/3fku_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[Hemagglutinin|Hemagglutinin]] | + | *[[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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Aird, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Ali, M]] | + | [[Category: Aird D]] |
| - | [[Category: Bankston, L A]] | + | [[Category: Ali M]] |
| - | [[Category: Cadwell, G]] | + | [[Category: Bankston LA]] |
| - | [[Category: Chen, L M]] | + | [[Category: Cadwell G]] |
| - | [[Category: Cox, N]] | + | [[Category: Chen LM]] |
| - | [[Category: Donis, R O]] | + | [[Category: Cox N]] |
| - | [[Category: Han, T]] | + | [[Category: Donis RO]] |
| - | [[Category: Hwang, W C]] | + | [[Category: Han T]] |
| - | [[Category: Liddington, R C]] | + | [[Category: Hwang WC]] |
| - | [[Category: Marasco, W A]] | + | [[Category: Liddington RC]] |
| - | [[Category: Murakami, A]] | + | [[Category: Marasco WA]] |
| - | [[Category: Perez, S]] | + | [[Category: Murakami A]] |
| - | [[Category: Santelli, E]] | + | [[Category: Perez S]] |
| - | [[Category: Stec, B]] | + | [[Category: Santelli E]] |
| - | [[Category: Sui, J]] | + | [[Category: Stec B]] |
| - | [[Category: Wei, G]] | + | [[Category: Sui J]] |
| - | [[Category: Yammanuru, A]] | + | [[Category: Wei G]] |
| - | [[Category: Cell membrane]]
| + | [[Category: Yammanuru A]] |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Envelope protein]]
| + | |
| - | [[Category: F10]]
| + | |
| - | [[Category: Fusion protein]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: H5]]
| + | |
| - | [[Category: Hemagglutinin]]
| + | |
| - | [[Category: Influenza]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Neutralizing antibody]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Scfv]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| - | [[Category: Virion]]
| + | |
| Structural highlights
Function
HEMA_I03A0 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.[HAMAP-Rule:MF_04072]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses.,Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA Nat Struct Mol Biol. 2009 Mar;16(3):265-73. Epub 2009 Feb 22. PMID:19234466[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009 Mar;16(3):265-73. Epub 2009 Feb 22. PMID:19234466 doi:10.1038/nsmb.1566
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