View source for 7sgd


==Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from GPC-I53-50 nanoparticle by localized reconstruction==
<StructureSection load='7sgd' size='340' side='right'caption='[[7sgd]], [[Resolution|resolution]] 3.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sgd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mammarenavirus_lassaense Mammarenavirus lassaense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SGD 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]] 3.97&#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=FUC:ALPHA-L-FUCOSE'>FUC</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=7sgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sgd OCA], [https://pdbe.org/7sgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sgd RCSB], [https://www.ebi.ac.uk/pdbsum/7sgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sgd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLYC_LASSJ GLYC_LASSJ] 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. The GP complex interacts with host glycosylated LAMP1 to mediate efficient infection.<ref>PMID:24970085</ref>   Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis.  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 (By similarity).
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== Publication Abstract from PubMed ==
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.

Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.,Brouwer PJM, Antanasijevic A, Ronk AJ, Muller-Krauter H, Watanabe Y, Claireaux M, Perrett HR, Bijl TPL, Grobben M, Umotoy JC, Schriek AI, Burger JA, Tejjani K, Lloyd NM, Steijaert TH, van Haaren MM, Sliepen K, de Taeye SW, van Gils MJ, Crispin M, Strecker T, Bukreyev A, Ward AB, Sanders RW Cell Host Microbe. 2022 Dec 14;30(12):1759-1772.e12. doi: , 10.1016/j.chom.2022.10.018. Epub 2022 Nov 17. PMID:36400021<ref>PMID:36400021</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mammarenavirus lassaense]]
[[Category: Antanasijevic A]]
[[Category: Brouwer PJM]]
[[Category: Ward AB]]