7uja
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7uja]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Respiratory_syncytial_virus Respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UJA FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uja]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Respiratory_syncytial_virus Respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UJA 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">Electron Microscopy, [[Resolution|Resolution]] 3.7Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=7uja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uja OCA], [https://pdbe.org/7uja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uja RCSB], [https://www.ebi.ac.uk/pdbsum/7uja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uja 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=7uja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uja OCA], [https://pdbe.org/7uja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uja RCSB], [https://www.ebi.ac.uk/pdbsum/7uja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uja ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/A0A218N9U8_HRSV A0A218N9U8_HRSV] Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.[ARBA:ARBA00035608] |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization. | + | Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum-neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization. |
| - | Rational | + | Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine.,Che Y, Gribenko AV, Song X, Handke LD, Efferen KS, Tompkins K, Kodali S, Nunez L, Prasad AK, Phelan LM, Ammirati M, Yu X, Lees JA, Chen W, Martinez L, Roopchand V, Han S, Qiu X, DeVincenzo JP, Jansen KU, Dormitzer PR, Swanson KA Sci Transl Med. 2023 Apr 26;15(693):eade6422. doi: 10.1126/scitranslmed.ade6422. , Epub 2023 Apr 26. PMID:37023209<ref>PMID:37023209</ref> |
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> | ||
Revision as of 11:37, 23 October 2024
Cryo-EM structure of Human respiratory syncytial virus F variant (construct pXCS847A)
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