4ubd: Difference between revisions
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==Crystal structure of a neutralizing human monoclonal antibody with 1968 H3 HA== | ==Crystal structure of a neutralizing human monoclonal antibody with 1968 H3 HA== | ||
<StructureSection load='4ubd' size='340' side='right' caption='[[4ubd]], [[Resolution|resolution]] 3.50Å' scene=''> | <StructureSection load='4ubd' size='340' side='right'caption='[[4ubd]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ubd]] is a 24 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=4UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UBD FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ubd]] is a 24 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=4UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UBD FirstGlance]. <br> | ||
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<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=4ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ubd OCA], [http://pdbe.org/4ubd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ubd RCSB], [http://www.ebi.ac.uk/pdbsum/4ubd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ubd 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=4ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ubd OCA], [http://pdbe.org/4ubd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ubd RCSB], [http://www.ebi.ac.uk/pdbsum/4ubd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ubd 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). | [[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). | ||
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==See Also== | ==See Also== | ||
*[[Hemagglutinin|Hemagglutinin]] | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] | ||
*[[3D structures | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: I68a4]] | [[Category: I68a4]] | ||
[[Category: Large Structures]] | |||
[[Category: Cho, M]] | [[Category: Cho, M]] | ||
[[Category: Donis, R O]] | [[Category: Donis, R O]] | ||
Revision as of 10:03, 4 March 2020
Crystal structure of a neutralizing human monoclonal antibody with 1968 H3 HACrystal structure of a neutralizing human monoclonal antibody with 1968 H3 HA
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 PubMedEffective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines. A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus.,Wu Y, Cho M, Shore D, Song M, Choi J, Jiang T, Deng YQ, Bourgeois M, Almli L, Yang H, Chen LM, Shi Y, Qi J, Li A, Yi KS, Chang M, Bae JS, Lee H, Shin J, Stevens J, Hong S, Qin CF, Gao GF, Chang SJ, Donis RO Nat Commun. 2015 Jul 21;6:7708. doi: 10.1038/ncomms8708. PMID:26196962[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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