View source for 7lbg


==CryoEM structure of the HCMV Trimer gHgLgO in complex with human Transforming growth factor beta receptor type 3 and neutralizing fabs 13H11 and MSL-109==
<StructureSection load='7lbg' size='340' side='right'caption='[[7lbg]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lbg]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5] 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=7LBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LBG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.6&#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=7lbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lbg OCA], [https://pdbe.org/7lbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lbg RCSB], [https://www.ebi.ac.uk/pdbsum/7lbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lbg ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== Publication Abstract from PubMed ==
Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRalpha) and transforming growth factor beta receptor 3 (TGFbetaR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRalpha and TGFbetaR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRalpha and TGFbetaR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRalpha interaction has an inhibitory effect on PDGFRalpha signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV.

Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry.,Kschonsak M, Rouge L, Arthur CP, Hoangdung H, Patel N, Kim I, Johnson MC, Kraft E, Rohou AL, Gill A, Martinez-Martin N, Payandeh J, Ciferri C Cell. 2021 Mar 4;184(5):1232-1244.e16. doi: 10.1016/j.cell.2021.01.036. Epub 2021 , Feb 23. PMID:33626330<ref>PMID:33626330</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 7lbg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[TGF-beta receptor 3D structures|TGF-beta receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human betaherpesvirus 5]]
[[Category: Human herpesvirus 5 strain Merlin]]
[[Category: Large Structures]]
[[Category: Arthur CP]]
[[Category: Ciferri C]]
[[Category: Gill A]]
[[Category: Hoangdung H]]
[[Category: Johnson M]]
[[Category: Kim I]]
[[Category: Kraft E]]
[[Category: Kschonsak M]]
[[Category: Martinez-Martin N]]
[[Category: Patel N]]
[[Category: Payandeh J]]
[[Category: Rohou AL]]
[[Category: Rouge L]]