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| | <SX load='6c5v' size='340' side='right' viewer='molstar' caption='[[6c5v]], [[Resolution|resolution]] 4.80Å' scene=''> | | <SX load='6c5v' size='340' side='right' viewer='molstar' caption='[[6c5v]], [[Resolution|resolution]] 4.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c5v]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebva8 Ebva8], [http://en.wikipedia.org/wiki/Ebvg Ebvg] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C5V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C5V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c5v]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Epstein-barr_virus_strain_ag876 Epstein-barr virus strain ag876], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_4 Human gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C5V 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=MAN:ALPHA-D-MANNOSE'>MAN</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">Electron Microscopy, [[Resolution|Resolution]] 4.8Å</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=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>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BXLF2, gH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10376 EBVG]), gL, BKRF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=82830 EBVA8]), BZLF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10376 EBVG])</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=6c5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5v OCA], [https://pdbe.org/6c5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c5v RCSB], [https://www.ebi.ac.uk/pdbsum/6c5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5v ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6c5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5v OCA], [http://pdbe.org/6c5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c5v RCSB], [http://www.ebi.ac.uk/pdbsum/6c5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/K9US75_EBVG K9US75_EBVG]] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane fusion is mediated by the fusion machinery composed of gB and the heterodimer gH/gL. May also be involved in the fusion between the virion envelope and the outer nuclear membrane during virion morphogenesis.[HAMAP-Rule:MF_04033] [[http://www.uniprot.org/uniprot/GP42_EBVG GP42_EBVG]] Plays a role in virion attachment to host B-lymphocytes, through binding to leukocyte antigen (HLA) class II and subsequently participates in fusion of the virion with host membranes. May act as a tropism switch that directs fusion with B-lymphocytes and inhibits fusion with epithelial cells (By similarity). [[http://www.uniprot.org/uniprot/GL_EBVA8 GL_EBVA8]] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Acts as a functional inhibitor of gH and maintains gH in an inhibited form. Upon binding to host integrins, gL dissociates from gH leading to activation of the viral fusion glycoproteins gB and gH. | + | [https://www.uniprot.org/uniprot/GL_EBVA8 GL_EBVA8] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Acts as a functional inhibitor of gH and maintains gH in an inhibited form. Upon binding to host integrins, gL dissociates from gH leading to activation of the viral fusion glycoproteins gB and gH. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Ebva8]] | + | [[Category: Epstein-barr virus strain ag876]] |
| - | [[Category: Ebvg]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Human gammaherpesvirus 4]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gray, M A]] | + | [[Category: Gray MA]] |
| - | [[Category: McElrath, M J]] | + | [[Category: McElrath MJ]] |
| - | [[Category: McGuire, A T]] | + | [[Category: McGuire AT]] |
| - | [[Category: Ortego, M S]] | + | [[Category: Ortego MS]] |
| - | [[Category: Pancera, M]] | + | [[Category: Pancera M]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Snijder J]] |
| - | [[Category: Snijder, J]] | + | [[Category: Stuart AB]] |
| - | [[Category: Stuart, A B]] | + | [[Category: Veesler D]] |
| - | [[Category: Veesler, D]] | + | [[Category: Weidle C]] |
| - | [[Category: Weidle, C]] | + | |
| - | [[Category: Epstein-barr virus]]
| + | |
| - | [[Category: Gh/gl]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Neutralizing antibody]]
| + | |
| - | [[Category: Ssgcid]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
GL_EBVA8 The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Acts as a functional inhibitor of gH and maintains gH in an inhibited form. Upon binding to host integrins, gL dissociates from gH leading to activation of the viral fusion glycoproteins gB and gH.
Publication Abstract from PubMed
Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden.
An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus.,Snijder J, Ortego MS, Weidle C, Stuart AB, Gray MD, McElrath MJ, Pancera M, Veesler D, McGuire AT Immunity. 2018 Apr 17;48(4):799-811.e9. doi: 10.1016/j.immuni.2018.03.026. PMID:29669253[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Snijder J, Ortego MS, Weidle C, Stuart AB, Gray MD, McElrath MJ, Pancera M, Veesler D, McGuire AT. An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. Immunity. 2018 Apr 17;48(4):799-811.e9. doi: 10.1016/j.immuni.2018.03.026. PMID:29669253 doi:http://dx.doi.org/10.1016/j.immuni.2018.03.026
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