View source for 5vob


==Crystal structure of HCMV Pentamer in complex with neutralizing antibody 8I21==
<StructureSection load='5vob' size='340' side='right'caption='[[5vob]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vob]] 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=5VOB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VOB 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5voc|5voc]], [[5vod|5vod]]</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]), IGKV3-15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5vob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vob OCA], [http://pdbe.org/5vob PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vob RCSB], [http://www.ebi.ac.uk/pdbsum/5vob PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vob ProSAT]</span></td></tr>
</table>
== 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>  
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== 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<ref>PMID:28783665</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5vob" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hcmv8]]
[[Category: Hcmva]]
[[Category: Hcmvm]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Chandramouli, S]]
[[Category: Malito, E]]
[[Category: Hcmv]]
[[Category: Immunogen]]
[[Category: Neutralizing epitope]]
[[Category: Pentamer]]
[[Category: Vaccine]]
[[Category: Viral entry]]
[[Category: Viral protein-immune system complex]]