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| | ==JUNV GP1 CR1-10 Fab CR1-28 Fab complex== | | ==JUNV GP1 CR1-10 Fab CR1-28 Fab complex== |
| - | <StructureSection load='5w1k' size='340' side='right' caption='[[5w1k]], [[Resolution|resolution]] 3.99Å' scene=''> | + | <StructureSection load='5w1k' size='340' side='right'caption='[[5w1k]], [[Resolution|resolution]] 3.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w1k]] is a 20 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W1K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w1k]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Argentinian_mammarenavirus Argentinian mammarenavirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W1K 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=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]] 3.99Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w1g|5w1g]], [[5w1m|5w1m]]</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=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=5w1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1k OCA], [http://pdbe.org/5w1k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1k RCSB], [http://www.ebi.ac.uk/pdbsum/5w1k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1k 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=5w1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1k OCA], [https://pdbe.org/5w1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w1k RCSB], [https://www.ebi.ac.uk/pdbsum/5w1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLYC_JUNIN GLYC_JUNIN]] 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 (By similarity). Glycoprotein G1 mediates virus attachment to host TFRC. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.<ref>PMID:19548229</ref> 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_JUNIN GLYC_JUNIN] 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 (By similarity). Glycoprotein G1 mediates virus attachment to host TFRC. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.<ref>PMID:19548229</ref> 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: Abraham, J]] | + | [[Category: Argentinian mammarenavirus]] |
| - | [[Category: Clark, L E]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Raymond, D D]] | + | [[Category: Large Structures]] |
| - | [[Category: Antibody]] | + | [[Category: Abraham J]] |
| - | [[Category: Arenavirus]] | + | [[Category: Clark LE]] |
| - | [[Category: Fab]] | + | [[Category: Raymond DD]] |
| - | [[Category: Junin virus]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
GLYC_JUNIN 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 (By similarity). Glycoprotein G1 mediates virus attachment to host TFRC. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] 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
While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.
Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.,Clark LE, Mahmutovic S, Raymond DD, Dilanyan T, Koma T, Manning JT, Shankar S, Levis SC, Briggiler AM, Enria DA, Wucherpfennig KW, Paessler S, Abraham J Nat Commun. 2018 May 14;9(1):1884. doi: 10.1038/s41467-018-04271-z. PMID:29760382[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Martinez MG, Forlenza MB, Candurra NA. Involvement of cellular proteins in Junin arenavirus entry. Biotechnol J. 2009 Jun;4(6):866-70. doi: 10.1002/biot.200800357. PMID:19548229 doi:http://dx.doi.org/10.1002/biot.200800357
- ↑ Clark LE, Mahmutovic S, Raymond DD, Dilanyan T, Koma T, Manning JT, Shankar S, Levis SC, Briggiler AM, Enria DA, Wucherpfennig KW, Paessler S, Abraham J. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses. Nat Commun. 2018 May 14;9(1):1884. doi: 10.1038/s41467-018-04271-z. PMID:29760382 doi:http://dx.doi.org/10.1038/s41467-018-04271-z
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