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Yorodumi- PDB-7uja: Cryo-EM structure of Human respiratory syncytial virus F variant ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7uja | ||||||
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Title | Cryo-EM structure of Human respiratory syncytial virus F variant (construct pXCS847A) | ||||||
Components |
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Keywords | VIRAL PROTEIN / RSV / RSVF / pre-fusion | ||||||
Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | ||||||
Biological species | Respiratory syncytial virus Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Lees, J.A. / Ammirati, M. / Han, S. | ||||||
Funding support | 1items
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Citation | Journal: Sci Transl Med / Year: 2023 Title: Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine. Authors: Ye Che / Alexey V Gribenko / Xi Song / Luke D Handke / Kari S Efferen / Kristin Tompkins / Srinivas Kodali / Lorna Nunez / A Krishna Prasad / Lynn M Phelan / Mark Ammirati / Xiaodi Yu / ...Authors: Ye Che / Alexey V Gribenko / Xi Song / Luke D Handke / Kari S Efferen / Kristin Tompkins / Srinivas Kodali / Lorna Nunez / A Krishna Prasad / Lynn M Phelan / Mark Ammirati / Xiaodi Yu / Joshua A Lees / Wei Chen / Lyndsey Martinez / Vidia Roopchand / Seungil Han / Xiayang Qiu / John P DeVincenzo / Kathrin U Jansen / Philip R Dormitzer / Kena A Swanson / Abstract: 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 ...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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7uja.cif.gz | 478.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7uja.ent.gz | 383.7 KB | Display | PDB format |
PDBx/mmJSON format | 7uja.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7uja_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7uja_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7uja_validation.xml.gz | 82.1 KB | Display | |
Data in CIF | 7uja_validation.cif.gz | 123.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uj/7uja ftp://data.pdbj.org/pub/pdb/validation_reports/uj/7uja | HTTPS FTP |
-Related structure data
Related structure data | 26562MC 7uj3C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RSV variant (construct pXCS847A) ... , 2 types, 6 molecules ACKPQR
#1: Protein | Mass: 45025.391 Da / Num. of mol.: 3 / Mutation: I145S, S187I, D483S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Respiratory syncytial virus / Production host: Mammalia (mammals) / References: UniProt: A0A7D5GVC1 #6: Protein | Mass: 12109.954 Da / Num. of mol.: 3 / Mutation: A100C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Respiratory syncytial virus / Production host: Mammalia (mammals) / References: UniProt: A0A7D5GVC1 |
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-Antibody , 4 types, 12 molecules BGLDHMEINFJO
#2: Antibody | Mass: 26231.088 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mammalia (mammals) #3: Antibody | Mass: 23972.656 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mammalia (mammals) #4: Antibody | Mass: 25989.154 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mammalia (mammals) #5: Antibody | Mass: 23273.938 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mammalia (mammals) |
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-Sugars , 1 types, 3 molecules
#7: Sugar |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Human respiratory syncytial virus F variant (construct pXCS847A) with Fabs AM14 and AM22 Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT | |||||||||||||||
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Source (natural) | Organism: Respiratory syncytial virus | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 5000 nm / Nominal defocus min: 500 nm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 20 sec. / Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 420325 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 183713 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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