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| | ==Structure of Human Monoclonal Antibody E317 Fab Complex with HSV-2 gD== | | ==Structure of Human Monoclonal Antibody E317 Fab Complex with HSV-2 gD== |
| - | <StructureSection load='3w9e' size='340' side='right' caption='[[3w9e]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3w9e' size='340' side='right'caption='[[3w9e]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3w9e]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-2 Hhv-2] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W9E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3w9e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_2_strain_HG52 Human herpesvirus 2 strain HG52]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W9E 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w9d|3w9d]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10315 HHV-2])</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=3w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w9e OCA], [https://pdbe.org/3w9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w9e RCSB], [https://www.ebi.ac.uk/pdbsum/3w9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w9e 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=3w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w9e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w9e RCSB], [http://www.ebi.ac.uk/pdbsum/3w9e PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GD_HHV2H GD_HHV2H]] Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and PVRL1. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity). | + | [https://www.uniprot.org/uniprot/GD_HHV2H GD_HHV2H] Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and PVRL1. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | 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 3w9e" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Monoclonal Antibody|Monoclonal Antibody]] | + | *[[Glycoproteins B and D|Glycoproteins B and D]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hhv-2]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Human herpesvirus 2 strain HG52]] |
| - | [[Category: Lee, C C]] | + | [[Category: Large Structures]] |
| - | [[Category: Lin, L L]] | + | [[Category: Lee CC]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Lin LL]] |
| - | [[Category: Igg fold]] | + | [[Category: Wang AHJ]] |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
GD_HHV2H Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and PVRL1. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity).
Publication Abstract from PubMed
Glycoprotein D (gD) of herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD-nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.
Structural basis for the antibody neutralization of herpes simplex virus.,Lee CC, Lin LL, Chan WE, Ko TP, Lai JS, Wang AH Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):1935-45. doi:, 10.1107/S0907444913016776. Epub 2013 Sep 20. PMID:24100313[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee CC, Lin LL, Chan WE, Ko TP, Lai JS, Wang AH. Structural basis for the antibody neutralization of herpes simplex virus. Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):1935-45. doi:, 10.1107/S0907444913016776. Epub 2013 Sep 20. PMID:24100313 doi:http://dx.doi.org/10.1107/S0907444913016776
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