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| | <StructureSection load='5vk2' size='340' side='right'caption='[[5vk2]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5vk2' size='340' side='right'caption='[[5vk2]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vk2]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lassj Lassj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VK2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vk2]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=5VK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VK2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.201Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GPC, GP-C ([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=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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vk2 OCA], [http://pdbe.org/5vk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vk2 RCSB], [http://www.ebi.ac.uk/pdbsum/5vk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vk2 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=5vk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vk2 OCA], [https://pdbe.org/5vk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vk2 RCSB], [https://www.ebi.ac.uk/pdbsum/5vk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vk2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lassj]] | + | [[Category: Lassa virus Josiah]] |
| - | [[Category: Branco, L M]] | + | [[Category: Branco LM]] |
| - | [[Category: Chandra, K]] | + | [[Category: Chandra K]] |
| - | [[Category: Garry, R F]] | + | [[Category: Garry RF]] |
| - | [[Category: Hastie, K M]] | + | [[Category: Hastie KM]] |
| - | [[Category: Kleinfelter, L M]] | + | [[Category: Kleinfelter LM]] |
| - | [[Category: Robinson, J E]] | + | [[Category: Robinson JE]] |
| - | [[Category: Rowland, M L]] | + | [[Category: Rowland ML]] |
| - | [[Category: Rowland, M M]] | + | [[Category: Rowland MM]] |
| - | [[Category: Saphire, E O]] | + | [[Category: Saphire EO]] |
| - | [[Category: Zandonatti, M A]] | + | [[Category: Zandonatti MA]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Arenavirus]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Lassa]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| 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
The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.
Structural basis for antibody-mediated neutralization of Lassa virus.,Hastie KM, Zandonatti MA, Kleinfelter LM, Heinrich ML, Rowland MM, Chandran K, Branco LM, Robinson JE, Garry RF, Saphire EO Science. 2017 Jun 2;356(6341):923-928. doi: 10.1126/science.aam7260. PMID:28572385[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Hastie KM, Zandonatti MA, Kleinfelter LM, Heinrich ML, Rowland MM, Chandran K, Branco LM, Robinson JE, Garry RF, Saphire EO. Structural basis for antibody-mediated neutralization of Lassa virus. Science. 2017 Jun 2;356(6341):923-928. doi: 10.1126/science.aam7260. PMID:28572385 doi:http://dx.doi.org/10.1126/science.aam7260
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