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| | <StructureSection load='5tdg' size='340' side='right'caption='[[5tdg]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='5tdg' size='340' side='right'caption='[[5tdg]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tdg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpt2 Bpt2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TDG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TDG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tdg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovine_orthopneumovirus Bovine orthopneumovirus] and [https://en.wikipedia.org/wiki/Escherichia_virus_T2 Escherichia virus T2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TDG FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tdl|5tdl]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">wac ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10664 BPT2])</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=5tdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tdg OCA], [https://pdbe.org/5tdg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tdg RCSB], [https://www.ebi.ac.uk/pdbsum/5tdg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tdg ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tdg OCA], [http://pdbe.org/5tdg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tdg RCSB], [http://www.ebi.ac.uk/pdbsum/5tdg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tdg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q76VI8_BPT2 Q76VI8_BPT2] [https://www.uniprot.org/uniprot/Q9YS24_9MONO Q9YS24_9MONO] |
| - | Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context. A "DS2" version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F. When challenged with a heterologous bovine respiratory syncytial virus, virus was not detected in nasal secretions nor in respiratory tract samples of DS2-immunized calves; by contrast bovine respiratory syncytial virus was detected in all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and for the prevention of bovine respiratory syncytial virus in calves.
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| - | | + | |
| - | Protection of calves by a prefusion-stabilized bovine RSV F vaccine.,Zhang B, Chen L, Silacci C, Thom M, Boyington JC, Druz A, Joyce MG, Guzman E, Kong WP, Lai YT, Stewart-Jones GBE, Tsybovsky Y, Yang Y, Zhou T, Baxa U, Mascola JR, Corti D, Lanzavecchia A, Taylor G, Kwong PD NPJ Vaccines. 2017 Mar 8;2:7. doi: 10.1038/s41541-017-0005-9. PMID:29021918<ref>PMID:29021918</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5tdg" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bpt2]] | + | [[Category: Bovine orthopneumovirus]] |
| | + | [[Category: Escherichia virus T2]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, L]] | + | [[Category: Chen L]] |
| - | [[Category: Kwong, P D]] | + | [[Category: Kwong PD]] |
| - | [[Category: Zhang, B]] | + | [[Category: Zhang B]] |
| - | [[Category: Bovine rsv f]]
| + | |
| - | [[Category: Prefusion stabilized]]
| + | |
| - | [[Category: Viral protein]]
| + | |
