8ve8: Difference between revisions
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The | ==Lineage IV Lassa virus glycoprotein (Josiah) in complex with rabbit polyclonal antibody (GP1-A epitope)== | ||
<StructureSection load='8ve8' size='340' side='right'caption='[[8ve8]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ve8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Lassa_virus_Josiah Lassa virus Josiah] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VE8 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]] 2.8Å</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=8ve8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ve8 OCA], [https://pdbe.org/8ve8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ve8 RCSB], [https://www.ebi.ac.uk/pdbsum/8ve8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ve8 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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design. | |||
Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses.,Brouwer PJM, Perrett HR, Beaumont T, Nijhuis H, Kruijer S, Burger JA, Bontjer I, Lee WH, Ferguson JA, Schauflinger M, Muller-Krauter H, Sanders RW, Strecker T, van Gils MJ, Ward AB Cell Rep. 2024 Sep 6;43(9):114708. doi: 10.1016/j.celrep.2024.114708. PMID:39243373<ref>PMID:39243373</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8ve8" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lassa virus Josiah]] | |||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Brouwer PJM]] | |||
[[Category: Perrett HR]] | |||
[[Category: Ward AB]] | |||