View source for 6jgy


==Crystal structure of LASV-GP2 in a post fusion conformation==
<StructureSection load='6jgy' size='340' side='right'caption='[[6jgy]], [[Resolution|resolution]] 3.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jgy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lassa_mammarenavirus Lassa mammarenavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JGY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.389&#8491;</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=6jgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jgy OCA], [https://pdbe.org/6jgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jgy RCSB], [https://www.ebi.ac.uk/pdbsum/6jgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jgy 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 ==
The envelope glycoproteins GP1 and GP2 of Lassa virus (LASV) bind to the host cell receptors to mediate viral infection. So far, no approved vaccines and specific treatment options against LASV exist. To develop specific fusion inhibitors against LASV, we solved the crystal structure of the post-fusion 6 helix bundle (6-HB) formed by two heptad repeat domains (HR1 and HR2) of GP2. This fusion core contains a parallel trimeric coiled-coil of three HR1 helices, around which three HR2 helices are entwined in an antiparallel manner. Various hydrophobic and charged interactions form between HR1 and HR2 domains to stabilize the overall conformation of GP2 fusion core. Based on the structure, we designed several peptides spanning the HR2 domain and tested their antiviral activities. We found that the longer HR2 peptides were effective in inhibiting LASV GPC protein-mediated cell-cell fusion under low pH condition. These results not only suggest that LASV infects the target cell mainly through endocytosis, including micropinocytosis, and membrane fusion at low pH, but also provide an important basis for rational design of LASV fusion inhibitors.

Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors.,Zhang X, Wang C, Chen B, Wang Q, Xu W, Ye S, Jiang S, Zhu Y, Zhang R Front Microbiol. 2019 Aug 13;10:1829. doi: 10.3389/fmicb.2019.01829. eCollection , 2019. PMID:31456769<ref>PMID:31456769</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jgy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glycoprotein GP 3D structures|Glycoprotein GP 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lassa mammarenavirus]]
[[Category: Chen B]]
[[Category: Ye S]]
[[Category: Zhang R]]
[[Category: Zhang X]]
[[Category: Zhu Y]]