View source for 4xhj


==gHgL of Varicella-zoster virus in complex with human neutralizing antibodies.==
<StructureSection load='4xhj' size='340' side='right'caption='[[4xhj]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xhj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_3_strain_Oka_vaccine Human herpesvirus 3 strain Oka vaccine]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XHJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.156&#8491;</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=4xhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xhj OCA], [https://pdbe.org/4xhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xhj RCSB], [https://www.ebi.ac.uk/pdbsum/4xhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xhj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GH_VZVO GH_VZVO] 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 of gD to one of its receptors, membrane fusion is mediated by the fusion machinery composed at least 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 (By similarity).
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== Publication Abstract from PubMed ==
Varicella-zoster virus (VZV), of the family Alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. The conserved herpesvirus glycoprotein gB and the heterodimer gHgL mediate virion envelope fusion with cell membranes during virus entry. Naturally occurring neutralizing antibodies against herpesviruses target these entry proteins. To determine the molecular basis for VZV neutralization, crystal structures of gHgL were determined in complex with fragments of antigen binding (Fabs) from two human monoclonal antibodies, IgG-94 and IgG-RC, isolated from seropositive subjects. These structures reveal that the antibodies target the same site, composed of residues from both gH and gL, distinct from two other neutralizing epitopes identified by negative-stain electron microscopy and mutational analysis. Inhibition of gB/gHgL-mediated membrane fusion and structural comparisons with herpesvirus homologs suggest that the IgG-RC/94 epitope is in proximity to the site on VZV gHgL that activates gB. Immunization studies proved that the anti-gHgL IgG-RC/94 epitope is a critical target for antibodies that neutralize VZV. Thus, the gHgL/Fab structures delineate a site of herpesvirus vulnerability targeted by natural immunity.

A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.,Xing Y, Oliver SL, Nguyen T, Ciferri C, Nandi A, Hickman J, Giovani C, Yang E, Palladino G, Grose C, Uematsu Y, Lilja AE, Arvin AM, Carfi A Proc Natl Acad Sci U S A. 2015 Apr 27. pii: 201501176. PMID:25918416<ref>PMID:25918416</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xhj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human herpesvirus 3 strain Oka vaccine]]
[[Category: Large Structures]]
[[Category: Xing Y]]