3whe - Revision history

OCA at 13:10, 8 November 2023

2023-11-08T13:10:55Z

← Older revision		Revision as of 13:10, 8 November 2023
Line 1:		Line 1:

	==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==		==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==
	<StructureSection load='3whe' size='340' side='right'caption='[[3whe]]' scene=''>		<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Aichi/2-1/1968(H3N2)) Influenza A virus (A/Aichi/2-1/1968(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>
	</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></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]] 4Å</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=MAN:ALPHA-D-MANNOSE'>MAN</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171-173, 239 and 240) and R (residues 91, 92, 270-273, 284 and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope including the glycan should be immunogenic in humans, and may induce production of broadly neutralizing antibodies against H3 viruses. IMPORTANCE: Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing Abs. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular receptor. As mutations are readily introduced into such epitopes, this type of antibody shows narrow strain specificity. Recently, however, broadly neutralizing antibodies have been isolated. Most of these bind either to conserved sites in the stem region or to the sialic acid-binding pocket itself. In the present study, we identified a new neutralizing epitope in the head region recognized by a broadly neutralizing human antibody against H3N2. This epitope may be useful for design of vaccines.

			Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses.,Iba Y, Fujii Y, Ohshima N, Sumida T, Kubota-Koketsu R, Ikeda M, Wakiyama M, Shirouzu M, Okada J, Okuno Y, Kurosawa Y, Yokoyama S J Virol. 2014 Apr 9. PMID:24719430<ref>PMID:24719430</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 3whe" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Hemagglutinin 3D structures\|Hemagglutinin 3D structures]]		*[[Hemagglutinin 3D structures\|Hemagglutinin 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fujii Y]]		[[Category: Fujii Y]]

OCA at 10:31, 31 August 2022

2022-08-31T10:31:41Z

← Older revision		Revision as of 10:31, 31 August 2022
Line 1:		Line 1:

	==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==		==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==
	<StructureSection load='3whe' size='340' side='right'caption='[[3whe]]~~, [[Resolution\|resolution]] 4.00Å~~' scene=''>		<StructureSection load='3whe' size='340' side='right'caption='[[3whe]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[3whe]] is a 36 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>
	</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe 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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
	~~== Function ==~~
	[[https://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171-173, 239 and 240) and R (residues 91, 92, 270-273, 284 and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope including the glycan should be immunogenic in humans, and may induce production of broadly neutralizing antibodies against H3 viruses. IMPORTANCE: Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing Abs. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular receptor. As mutations are readily introduced into such epitopes, this type of antibody shows narrow strain specificity. Recently, however, broadly neutralizing antibodies have been isolated. Most of these bind either to conserved sites in the stem region or to the sialic acid-binding pocket itself. In the present study, we identified a new neutralizing epitope in the head region recognized by a broadly neutralizing human antibody against H3N2. This epitope may be useful for design of vaccines.

	Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses.,Iba Y, Fujii Y, Ohshima N, Sumida T, Kubota-Koketsu R, Ikeda M, Wakiyama M, Shirouzu M, Okada J, Okuno Y, Kurosawa Y, Yokoyama S J Virol. 2014 Apr 9. PMID:24719430<ref>PMID:24719430</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3whe" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Hemagglutinin 3D structures\|Hemagglutinin 3D structures]]		*[[Hemagglutinin 3D structures\|Hemagglutinin 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fujii, Y]]		[[Category: Fujii Y]]
	[[Category: Shirouzu, M]]		[[Category: Shirouzu M]]
	[[Category: Sumida, T]]		[[Category: Sumida T]]
	[[Category: Yokoyama, S]]		[[Category: Yokoyama S]]
	~~[[Category: Viral protein-immune system complex~~]]

OCA at 04:57, 25 August 2022

2022-08-25T04:57:46Z

← Older revision		Revision as of 04:57, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>		<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure ~~with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE FirstGlance]. <br>
	</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe 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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
Line 26:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Human]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fujii, Y]]		[[Category: Fujii, Y]]

OCA at 05:36, 3 August 2022

2022-08-03T05:36:52Z

← Older revision		Revision as of 05:36, 3 August 2022
Line 3:		Line 3:
	<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>		<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human] and [~~http~~://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3WHE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WHE 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=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</scene>, <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene></td></tr>		</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [~~http~~://pdbe.org/3whe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3whe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe 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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [https://pdbe.org/3whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [https://www.ebi.ac.uk/pdbsum/3whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]		[[https://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:20, 13 November 2019

2019-11-13T11:20:50Z

← Older revision		Revision as of 11:20, 13 November 2019
Line 1:		Line 1:
	~~{{Large structure}}~~
	==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==		==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==
	<StructureSection load='3whe' size='340' side='right' caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>		<StructureSection load='3whe' size='340' side='right'caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WHE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WHE 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>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</scene></td></tr>		</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=MAN:ALPHA-D-MANNOSE'>MAN</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">126567434, HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [http://pdbe.org/3whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [http://www.ebi.ac.uk/pdbsum/3whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe 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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [http://pdbe.org/3whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [http://www.ebi.ac.uk/pdbsum/3whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
	~~{{Large structure}}~~
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]		[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 3whe" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3whe" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Hemagglutinin 3D structures\|Hemagglutinin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Fujii, Y]]		[[Category: Fujii, Y]]
	[[Category: Shirouzu, M]]		[[Category: Shirouzu, M]]

OCA at 06:41, 5 August 2016

2016-08-05T06:41:03Z

← Older revision		Revision as of 06:41, 5 August 2016
Line 1:		Line 1:
			{{Large structure}}
	==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==		==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==
	<StructureSection load='3whe' size='340' side='right' caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>		<StructureSection load='3whe' size='340' side='right' caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
Line 5:		Line 6:
	</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [http://www.ebi.ac.uk/pdbsum/3whe PDBsum]</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [http://pdbe.org/3whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [http://www.ebi.ac.uk/pdbsum/3whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3whe ProSAT]</span></td></tr>
	</table>		</table>
			{{Large structure}}
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]		[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
Line 17:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3whe" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:35, 25 December 2014

2014-12-25T16:35:59Z

← Older revision		Revision as of 16:35, 25 December 2014
Line 1:		Line 1:
	~~{{Large structure}}~~		==A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses==
	~~{{STRUCTURE_3whe\| PDB=3whe \| SCENE= }}~~		<StructureSection load='3whe' size='340' side='right' caption='[[3whe]], [[Resolution\|resolution]] 4.00Å' scene=''>
	===A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses===		== Structural highlights ==
	~~{{ABSTRACT_PUBMED_24719430}}~~		<table><tr><td colspan='2'>[[3whe]] is a 36 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/aichi/2-1/1968(h3n2)) Influenza a virus (a/aichi/2-1/1968(h3n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WHE 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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	==Function==		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">126567434, HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1391655 Influenza A virus (A/Aichi/2-1/1968(H3N2))])</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=3whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3whe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3whe RCSB], [http://www.ebi.ac.uk/pdbsum/3whe PDBsum]</span></td></tr>
			</table>
			== Function ==
	[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]		[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171-173, 239 and 240) and R (residues 91, 92, 270-273, 284 and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope including the glycan should be immunogenic in humans, and may induce production of broadly neutralizing antibodies against H3 viruses. IMPORTANCE: Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing Abs. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular receptor. As mutations are readily introduced into such epitopes, this type of antibody shows narrow strain specificity. Recently, however, broadly neutralizing antibodies have been isolated. Most of these bind either to conserved sites in the stem region or to the sialic acid-binding pocket itself. In the present study, we identified a new neutralizing epitope in the head region recognized by a broadly neutralizing human antibody against H3N2. This epitope may be useful for design of vaccines.

	~~==About this Structure==~~		Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses.,Iba Y, Fujii Y, Ohshima N, Sumida T, Kubota-Koketsu R, Ikeda M, Wakiyama M, Shirouzu M, Okada J, Okuno Y, Kurosawa Y, Yokoyama S J Virol. 2014 Apr 9. PMID:24719430<ref>PMID:24719430</ref>
	~~[[3whe]] is a 36 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=3WHE OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group="xtra">PMID:024719430</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>
	[[Category: Fujii, Y.]]		== References ==
	[[Category: Shirouzu, M.]]		<references/>
	[[Category: Sumida, T.]]		__TOC__
	[[Category: Yokoyama, S.]]		</StructureSection>
			[[Category: Human]]
			[[Category: Fujii, Y]]
			[[Category: Shirouzu, M]]
			[[Category: Sumida, T]]
			[[Category: Yokoyama, S]]
	[[Category: Viral protein-immune system complex]]		[[Category: Viral protein-immune system complex]]

OCA at 07:44, 23 April 2014

2014-04-23T07:44:17Z

← Older revision		Revision as of 07:44, 23 April 2014
Line 1:		Line 1:
	~~'''Unreleased~~ structure~~'''~~		{{Large structure}}
			{{STRUCTURE_3whe\| PDB=3whe \| SCENE= }}
			===A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses===
			{{ABSTRACT_PUBMED_24719430}}

	~~The entry 3whe is ON HOLD until Paper Publication~~		==Function==
			[[http://www.uniprot.org/uniprot/T2HNI1_9INFA T2HNI1_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:SAAS000149_004_327643]

	~~Authors~~: ~~Fujii, Y~~.~~, Sumida, T~~.~~, Shirouzu, M~~.~~, Yokoyama, S~~.		==About this Structure==
			[[3whe]] is a 36 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WHE OCA].

	~~Description~~: ~~A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses~~		==Reference==
			<ref group="xtra">PMID:024719430</ref><references group="xtra"/><references/>
			[[Category: Fujii, Y.]]
			[[Category: Shirouzu, M.]]
			[[Category: Sumida, T.]]
			[[Category: Yokoyama, S.]]
			[[Category: Viral protein-immune system complex]]

OCA at 06:28, 2 October 2013

2013-10-02T06:28:12Z

← Older revision		Revision as of 06:28, 2 October 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3whe is ON HOLD		The entry 3whe is ON HOLD until Paper Publication

	Authors: Fujii, Y., Sumida, T., Shirouzu, M., Yokoyama, S.		Authors: Fujii, Y., Sumida, T., Shirouzu, M., Yokoyama, S.

	Description: A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses		Description: A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses

OCA at 03:14, 20 September 2013

2013-09-20T03:14:05Z

← Older revision		Revision as of 03:14, 20 September 2013
Line 3:		Line 3:
	The entry 3whe is ON HOLD		The entry 3whe is ON HOLD

	Authors: Fujii, Y, Sumida, T, Shirouzu, M, Yokoyama, S		Authors: Fujii, Y., Sumida, T., Shirouzu, M., Yokoyama, S.

	Description: A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses		Description: A new conserved neutralizing epitope at the globular head of hemagglutinin in H3N2 influenza viruses