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| | ==Crystal structure of GP1 - the receptor binding domain of Lassa virus== | | ==Crystal structure of GP1 - the receptor binding domain of Lassa virus== |
| - | <StructureSection load='4zjf' size='340' side='right'caption='[[4zjf]], [[Resolution|resolution]] 2.59Å' scene=''> | + | <StructureSection load='4zjf' size='340' side='right'caption='[[4zjf]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zjf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lassj Lassj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zjf]] is a 4 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=4ZJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.595Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GPC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11622 LASSJ])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjf OCA], [http://pdbe.org/4zjf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zjf RCSB], [http://www.ebi.ac.uk/pdbsum/4zjf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zjf ProSAT]</span></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=4zjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjf OCA], [https://pdbe.org/4zjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zjf RCSB], [https://www.ebi.ac.uk/pdbsum/4zjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zjf ProSAT]</span></td></tr> |
| | </table> | | </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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[GP1 of Lassa Virus|GP1 of Lassa Virus]]
| + | *[[Glycoprotein GP 3D structures|Glycoprotein GP 3D structures]] |
| - | *[[Glycoprotein GP|Glycoprotein GP]] | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lassj]] | + | [[Category: Lassa virus Josiah]] |
| - | [[Category: Cohen, N]] | + | [[Category: Cohen N]] |
| - | [[Category: Cohen-Dvashi, H]] | + | [[Category: Cohen-Dvashi H]] |
| - | [[Category: Diskin, R]] | + | [[Category: Diskin R]] |
| - | [[Category: Israeli, H]] | + | [[Category: Israeli H]] |
| - | [[Category: Arenaviruse]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Lassa]]
| + | |
| - | [[Category: Receptor binding]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
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.[1] 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).
Publication Abstract from PubMed
Lassa virus is a notorious human pathogen that infects many thousands of people each year in West Africa, causing severe viral hemorrhagic fevers and significant mortality. The surface glycoprotein of Lassa virus mediates receptor recognition through its GP1 subunit. Here we report the crystal structure of GP1 from Lassa virus, which is the first representative GP1 structure for Old World arenaviruses. We identify a unique triad of histidines that forms a binding site for LAMP1, a known lysosomal protein recently discovered to be a critical receptor for internalized Lassa virus at acidic pH. We demonstrate that mutation of this histidine-triad, which is highly conserved among Old World arenaviruses, impairs LAMP1 recognition. Our biochemical and structural data further suggest that GP1 from Lassa may undergo irreversible conformational changes that could serve as an immunological decoy mechanism. Together with a variable region that we identify on the surface of GP1, those could be two distinct mechanisms that Lassa virus utilizes to avoid antibody-based immune response. IMPORTANCE: Structural data at atomic resolution for viral proteins is key for understanding their function at the molecular level and can facilitate novel avenues for combating viral infections. Here we use X-ray protein crystallography to decipher the crystal structure of the receptor-binding domain (GP1) from Lassa virus. This is a pathogenic virus that causes significant illness and mortality in West Africa. This structure reveals the overall architecture of GP1 domains from the group of viruses known as the Old World arenaviruses. Using this structural information we elucidate the pH switch and binding mechanisms of Lassa virus to LAMP1, a recently identified host receptor that is critical for successful infection. Lastly, our structural analysis suggests two novel immune evasion mechanisms that Lassa virus may utilize to escape antibody-based immune response.
Molecular mechanism for LAMP1 recognition by Lassa Virus.,Cohen-Dvashi H, Cohen N, Israeli H, Diskin R J Virol. 2015 May 13. pii: JVI.00651-15. PMID:25972533[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jae LT, Raaben M, Herbert AS, Kuehne AI, Wirchnianski AS, Soh TK, Stubbs SH, Janssen H, Damme M, Saftig P, Whelan SP, Dye JM, Brummelkamp TR. Virus entry. Lassa virus entry requires a trigger-induced receptor switch. Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480. PMID:24970085 doi:http://dx.doi.org/10.1126/science.1252480
- ↑ Cohen-Dvashi H, Cohen N, Israeli H, Diskin R. Molecular mechanism for LAMP1 recognition by Lassa Virus. J Virol. 2015 May 13. pii: JVI.00651-15. PMID:25972533 doi:http://dx.doi.org/10.1128/JVI.00651-15
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