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| | ==Crystal structure of broadly neutralizing antibody 13D4 bound to H5N1 influenza hemagglutinin, HA head region== | | ==Crystal structure of broadly neutralizing antibody 13D4 bound to H5N1 influenza hemagglutinin, HA head region== |
| - | <StructureSection load='6a0z' size='340' side='right' caption='[[6a0z]], [[Resolution|resolution]] 2.33Å' scene=''> | + | <StructureSection load='6a0z' size='340' side='right'caption='[[6a0z]], [[Resolution|resolution]] 2.33Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6a0z]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A0Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6a0z]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/chicken/Chachoengsao/Thailand/CU-11/04(H5N1)) Influenza A virus (A/chicken/Chachoengsao/Thailand/CU-11/04(H5N1))] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A0Z 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]] 2.329Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></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>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=11676 9HIV1])</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=6a0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a0z OCA], [https://pdbe.org/6a0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a0z RCSB], [https://www.ebi.ac.uk/pdbsum/6a0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a0z 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=6a0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a0z OCA], [http://pdbe.org/6a0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a0z RCSB], [http://www.ebi.ac.uk/pdbsum/6a0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a0z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q45ZR9_9INFA Q45ZR9_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:SAAS01039674] 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/M1E1E4_9HIV1 M1E1E4_9HIV1] [https://www.uniprot.org/uniprot/Q6DQ34_9INFA Q6DQ34_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:SAAS008980_004_327643] |
| | <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 6a0z" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6a0z" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Human immunodeficiency virus 1]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Li, S]] | + | [[Category: Li S]] |
| - | [[Category: Li, T]] | + | [[Category: Li T]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Immune complex]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
M1E1E4_9HIV1 Q6DQ34_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:SAAS008980_004_327643]
Publication Abstract from PubMed
Human infection with highly pathogenic avian influenza A viruses lead to cause severe diseases and fatalities. We previously identified a potent and broad-neutralizing antibody (bnAb), 13D4, against the H5N1 virus. Here, we report the co-crystal structure of 13D4 in complex with the hemagglutinin of A/Vietnam/1194/2004 (H5N1). We show that the heavy chain complementarity determining region 3 (HCDR3) of 13D4 confers H5N1 broad yet specific neutralization against H5N1, undergoing conformational rearrangement to bind to the receptor-binding site (RBS). Further, we show that mutating four critical residues within the RBS-Trp153, Lys156, Lys193, Leu194-disrupts the binding between 13D4 and HA. Viruses bearing Asn193 instead of Lys/Arg can evade 13D4 neutralization, indicating that Lys193 polymorphism might be, at least in part, involved in the antigenicity of recent H5 genotypes (such as H5N6 and H5N8) distinguished from H5N1. BnAb 13D4 may offers a template for therapeutic RBS-inhibitor design and serve as an indicator of antigenic change of current H5 viruses.IMPORTANCE The infection of highly pathogenic avian influenza A virus remains a threat for public health. Our broad-neutralizing antibody, 13D4, is capable of neutralizing all representative H5N1 viruses and protecting mice against lethal challenge. Structural analysis revealed that 13D4 uses the heavy chain complementarity determining region 3 (HCDR3) to fit to receptor binding site (RBS) via conformational rearrangement. Four conserved residues within the RBS are critical for the broad potency of 13D4. Importantly, polymorphism of Lys193 on RBS may be associated with the antigenicity shift from H5N1 to other new emerging viruses, such as H5N6 and H5N8. Our findings may pave a way for highly pathogenic avian influenza vaccine development and therapeutic RBS-inhibitor design.
Structural Basis for the Broad, Antibody-Mediated Neutralization of H5N1 Influenza Virus.,Lin Q, Li T, Chen Y, Lau SY, Wei M, Zhang Y, Zhang Z, Yao Q, Li J, Li Z, Wang D, Zheng Q, Yu H, Gu Y, Zhang J, Chen H, Li S, Xia N J Virol. 2018 Jun 20. pii: JVI.00547-18. doi: 10.1128/JVI.00547-18. PMID:29925655[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin Q, Li T, Chen Y, Lau SY, Wei M, Zhang Y, Zhang Z, Yao Q, Li J, Li Z, Wang D, Zheng Q, Yu H, Gu Y, Zhang J, Chen H, Li S, Xia N. Structural Basis for the Broad, Antibody-Mediated Neutralization of H5N1 Influenza Virus. J Virol. 2018 Jun 20. pii: JVI.00547-18. doi: 10.1128/JVI.00547-18. PMID:29925655 doi:http://dx.doi.org/10.1128/JVI.00547-18
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