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| | <StructureSection load='5vod' size='340' side='right'caption='[[5vod]], [[Resolution|resolution]] 5.90Å' scene=''> | | <StructureSection load='5vod' size='340' side='right'caption='[[5vod]], [[Resolution|resolution]] 5.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vod]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcmv8 Hcmv8], [http://en.wikipedia.org/wiki/Hcmva Hcmva], [http://en.wikipedia.org/wiki/Hcmvm Hcmvm] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VOD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VOD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vod]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_5508 Human herpesvirus 5 strain 5508], [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_AD169 Human herpesvirus 5 strain AD169] and [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_Merlin Human herpesvirus 5 strain Merlin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VOD 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">X-ray diffraction, [[Resolution|Resolution]] 5.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cob|5cob]], [[5voc|5voc]]</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">gH, UL75 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=295027 HCMVM]), gL, UL115 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=69168 HCMV8]), UL128 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10360 HCMVA]), UL130 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=295027 HCMVM]), UL131A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=295027 HCMVM])</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=5vod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vod OCA], [https://pdbe.org/5vod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vod RCSB], [https://www.ebi.ac.uk/pdbsum/5vod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vod 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=5vod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vod OCA], [http://pdbe.org/5vod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vod RCSB], [http://www.ebi.ac.uk/pdbsum/5vod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vod ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GL_HCMV8 GL_HCMV8]] 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. [[http://www.uniprot.org/uniprot/GH_HCMVM GH_HCMVM]] 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. [[http://www.uniprot.org/uniprot/U131A_HCMVM U131A_HCMVM]] Plays an essential role in endothelial cell entry and release steps. Contributes to the formation of the complex between UL128, UL130 and gH-gL.<ref>PMID:16894182</ref> <ref>PMID:22031943</ref> | + | [https://www.uniprot.org/uniprot/GH_HCMVM GH_HCMVM] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hcmv8]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hcmva]] | + | [[Category: Human herpesvirus 5 strain 5508]] |
| - | [[Category: Hcmvm]] | + | [[Category: Human herpesvirus 5 strain AD169]] |
| - | [[Category: Human]] | + | [[Category: Human herpesvirus 5 strain Merlin]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chandramouli, S]] | + | [[Category: Chandramouli S]] |
| - | [[Category: Malito, E]] | + | [[Category: Malito E]] |
| - | [[Category: Hcmv]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunogen]]
| + | |
| - | [[Category: Neutralizing epitope]]
| + | |
| - | [[Category: Pentamer]]
| + | |
| - | [[Category: Vaccine]]
| + | |
| - | [[Category: Viral entry]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
5vod is a 7 chain structure with sequence from Homo sapiens, Human herpesvirus 5 strain 5508, Human herpesvirus 5 strain AD169 and Human herpesvirus 5 strain Merlin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 5.9Å |
| Ligands: | , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GH_HCMVM 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.
Publication Abstract from PubMed
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 A resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a beta hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.
Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.,Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, Carfi A Sci Immunol. 2017 Jun 30;2(12). pii: eaan1457. doi: 10.1126/sciimmunol.aan1457. PMID:28783665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, Carfi A. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Sci Immunol. 2017 Jun 30;2(12). pii: eaan1457. doi: 10.1126/sciimmunol.aan1457. PMID:28783665 doi:http://dx.doi.org/10.1126/sciimmunol.aan1457
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