+Open data
-Basic information
Entry | Database: PDB / ID: 8v5a | ||||||
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Title | Prefusion-stabilized Respirovirus type 3 Fusion protein | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / fusion protein / viral glycoprotein / membrane fusion / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | ||||||
Biological species | Human respirovirus 3 Lama glama (llama) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Johnson, N.V. / McLellan, J.S. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein. Authors: Johannes P M Langedijk / Freek Cox / Nicole V Johnson / Daan van Overveld / Lam Le / Ward van den Hoogen / Richard Voorzaat / Roland Zahn / Leslie van der Fits / Jarek Juraszek / Jason S ...Authors: Johannes P M Langedijk / Freek Cox / Nicole V Johnson / Daan van Overveld / Lam Le / Ward van den Hoogen / Richard Voorzaat / Roland Zahn / Leslie van der Fits / Jarek Juraszek / Jason S McLellan / Mark J G Bakkers / Abstract: The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as ...The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8v5a.cif.gz | 310.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8v5a.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8v5a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8v5a_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8v5a_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8v5a_validation.xml.gz | 57.2 KB | Display | |
Data in CIF | 8v5a_validation.cif.gz | 84.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/v5/8v5a ftp://data.pdbj.org/pub/pdb/validation_reports/v5/8v5a | HTTPS FTP |
-Related structure data
Related structure data | 42981MC 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
#1: Protein | Mass: 54147.891 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human respirovirus 3 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: A0A023PFZ0 #2: Antibody | Mass: 12487.816 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli) |
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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: Trimeric Human Respirovirus 3 Fusion Protein bound to 3 copies of nanobody 4C06 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.2325 MDa / Experimental value: NO |
Source (natural) | Organism: Human respirovirus 3 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.18.2_3874: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 193265 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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