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| | ==Crystal structure of DENV1-E111 single chain variable fragment bound to DENV-1 DIII, strain 16007.== | | ==Crystal structure of DENV1-E111 single chain variable fragment bound to DENV-1 DIII, strain 16007.== |
| - | <StructureSection load='4ffy' size='340' side='right' caption='[[4ffy]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4ffy' size='340' side='right'caption='[[4ffy]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ffy]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FFY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ffy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FFY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3irc|3irc]], [[4ffz|4ffz]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Envelope domain III ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11053 Dengue virus 1])</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=4ffy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffy OCA], [https://pdbe.org/4ffy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ffy RCSB], [https://www.ebi.ac.uk/pdbsum/4ffy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ffy ProSAT]</span></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=4ffy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ffy RCSB], [http://www.ebi.ac.uk/pdbsum/4ffy PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ffy" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Dengue virus 1]] | | [[Category: Dengue virus 1]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Austin, S K]] | + | [[Category: Austin SK]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Fremont DH]] |
| - | [[Category: Fremont, D H]] | + | [[Category: Nelson CA]] |
| - | [[Category: Nelson, C A]] | + | |
| - | [[Category: Antibody epitope]]
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| - | [[Category: Csgid]]
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| - | [[Category: Dengue virus]]
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| - | [[Category: Flavivirus]]
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| - | [[Category: Immune system]]
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| - | [[Category: Immune system-viral protein complex]]
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| - | [[Category: National institute of allergy and infectious disease]]
| + | |
| - | [[Category: Niaid]]
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| - | [[Category: Viral envelope protein]]
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| Structural highlights
Publication Abstract from PubMed
We previously developed a panel of neutralizing monoclonal antibodies against Dengue virus (DENV)-1, of which few exhibited inhibitory activity against all DENV-1 genotypes. This finding is consistent with reports observing variable neutralization of different DENV strains and genotypes using serum from individuals that experienced natural infection or immunization. Herein, we describe the crystal structures of DENV1-E111 bound to a novel CC' loop epitope on domain III (DIII) of the E protein from two different DENV-1 genotypes. Docking of our structure onto the available cryo-electron microscopy models of DENV virions revealed that the DENV1-E111 epitope was inaccessible, suggesting that this antibody recognizes an uncharacterized virus conformation. While the affinity of binding between DENV1-E111 and DIII varied by genotype, we observed limited correlation with inhibitory activity. Instead, our results support the conclusion that potent neutralization depends on genotype-dependent exposure of the CC' loop epitope. These findings establish new structural complexity of the DENV virion, which may be relevant for the choice of DENV strain for induction or analysis of neutralizing antibodies in the context of vaccine development.
Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope.,Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, Fremont DH PLoS Pathog. 2012 Oct;8(10):e1002930. doi: 10.1371/journal.ppat.1002930. Epub, 2012 Oct 4. PMID:23055922[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, Fremont DH. Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope. PLoS Pathog. 2012 Oct;8(10):e1002930. doi: 10.1371/journal.ppat.1002930. Epub, 2012 Oct 4. PMID:23055922 doi:http://dx.doi.org/10.1371/journal.ppat.1002930
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