View source for 7pvd


==Structure of the membrane soluble spike complex from the Lassa virus in a C1-symmetric map focused on the ectodomain==
<StructureSection load='7pvd' size='340' side='right'caption='[[7pvd]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pvd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lassa_virus_Josiah Lassa virus Josiah]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PVD 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]] 3.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BDP:BETA-D-GLUCOPYRANURONIC+ACID'>BDP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</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=7pvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pvd OCA], [https://pdbe.org/7pvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pvd RCSB], [https://www.ebi.ac.uk/pdbsum/7pvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pvd 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 ==
Lassa virus (LASV) is a human pathogen, causing substantial morbidity and mortality(1,2). Similar to other Arenaviridae, it presents a class-I spike complex on its surface that facilitates cell entry. The virus's cellular receptor is matriglycan, a linear carbohydrate that is present on alpha-dystroglycan(3,4), but the molecular mechanism that LASV uses to recognize this glycan is unknown. In addition, LASV and other arenaviruses have a unique signal peptide that forms an integral and functionally important part of the mature spike(5-8); yet the structure, function and topology of the signal peptide in the membrane remain uncertain(9-11). Here we solve the structure of a complete native LASV spike complex, finding that the signal peptide crosses the membrane once and that its amino terminus is located in the extracellular region. Together with a double-sided domain-switching mechanism, the signal peptide helps to stabilize the spike complex in its native conformation. This structure reveals that the LASV spike complex is preloaded with matriglycan, suggesting the mechanism of binding and rationalizing receptor recognition by alpha-dystroglycan-tropic arenaviruses. This discovery further informs us about the mechanism of viral egress and may facilitate the rational design of novel therapeutics that exploit this binding site.

Structure and receptor recognition by the Lassa virus spike complex.,Katz M, Weinstein J, Eilon-Ashkenazy M, Gehring K, Cohen-Dvashi H, Elad N, Fleishman SJ, Diskin R Nature. 2022 Mar;603(7899):174-179. doi: 10.1038/s41586-022-04429-2. Epub 2022 , Feb 16. PMID:35173332<ref>PMID:35173332</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: Lassa virus Josiah]]
[[Category: Diskin R]]
[[Category: Katz M]]