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6c5v

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An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus

6c5v, resolution 4.80Å

Structural highlights

6c5v is a 5 chain structure with sequence from Ebva8, Ebvg and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	BXLF2, gH (EBVG), gL, BKRF2 (EBVA8), BZLF2 (EBVG)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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] [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). [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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6c5v"

@@ Line 1: / Line 1: @@
 ==An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus==
-<StructureSection load='6c5v' size='340' side='right'caption='[[6c5v]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
+<SX load='6c5v' size='340' side='right' viewer='molstar' caption='[[6c5v]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
 == 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C5V FirstGlance]. <br>
+<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>
-</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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='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'>[http://oca.weizmann.ac.il/oca-docs/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>
+<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>
 == Function ==
@@ Line 26: / Line 26: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Ebva8]]
 [[Category: Ebvg]]

6c5v

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Current revision

An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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