View source for 8dmh


==Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28==
<StructureSection load='8dmh' size='340' side='right'caption='[[8dmh]], [[Resolution|resolution]] 3.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dmh]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mammarenavirus_choriomeningitidis Mammarenavirus choriomeningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DMH 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]] 3.19&#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=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=8dmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dmh OCA], [https://pdbe.org/8dmh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dmh RCSB], [https://www.ebi.ac.uk/pdbsum/8dmh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dmh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLYC_LYCVA GLYC_LYCVA] Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.<ref>PMID:17376927</ref>   Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis.<ref>PMID:9851928</ref>   Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome.<ref>PMID:8291229</ref> 
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== Publication Abstract from PubMed ==
The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.5C-M28 (M28). Additionally, we show that passive administration of M28, either as a prophylactic or therapeutic, protects mice from LCMV clone 13 (LCMV(cl13)) challenge. Our study illuminates not only the overall structural organization of LCMV GP and the mechanism for its inhibition by M28 but also presents a promising therapeutic candidate to prevent severe or fatal disease in individuals who are at risk of infection by a virus that poses a threat worldwide.

Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.,Moon-Walker A, Zhang Z, Zyla DS, Buck TK, Li H, Diaz Avalos R, Schendel SL, Hastie KM, Crotty S, Saphire EO Cell Chem Biol. 2023 Apr 20;30(4):403-411.e4. doi: , 10.1016/j.chembiol.2023.03.005. Epub 2023 Mar 28. PMID:36990092<ref>PMID:36990092</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dmh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mammarenavirus choriomeningitidis]]
[[Category: Hastie KM]]
[[Category: Moon-Walker A]]
[[Category: Saphire EO]]
[[Category: Zyla DS]]