4xi5
From Proteopedia
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| - | ''' | + | ==gHgL of varicella-zoster virus in complex with human neutralizing antibodies== |
| + | <StructureSection load='4xi5' size='340' side='right' caption='[[4xi5]], [[Resolution|resolution]] 3.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4xi5]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XI5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XI5 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> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xhj|4xhj]]</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=4xi5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xi5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xi5 RCSB], [http://www.ebi.ac.uk/pdbsum/4xi5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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). [[http://www.uniprot.org/uniprot/GL_VZVO GL_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, membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Xing, Y]] | [[Category: Xing, Y]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Neutralization epitope]] | ||
| + | [[Category: Viral protein-immune system complex]] | ||
Revision as of 12:11, 13 May 2015
gHgL of varicella-zoster virus in complex with human neutralizing antibodies
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