[English] 日本語
Yorodumi- PDB-8v5k: Structure of the Human Respirovirus 3 Fusion Protein Bound to Cam... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8v5k | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of the Human Respirovirus 3 Fusion Protein Bound to Camelid Nanobodies 4C03 and 4C06 | ||||||
Components |
| ||||||
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / viral fusion protein / camelid nanobodies / 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: 2.6 Å | ||||||
Authors | Johnson, N.V. / Ramamohan, A.R. / McLellan, J.S. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2024 Title: Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies. Authors: Nicole V Johnson / Revina C van Scherpenzeel / Mark J G Bakkers / Ajit R Ramamohan / Daan van Overveld / Lam Le / Johannes P M Langedijk / Joost A Kolkman / Jason S McLellan / Abstract: Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion ...Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8v5k.cif.gz | 382.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8v5k.ent.gz | 308.2 KB | Display | PDB format |
PDBx/mmJSON format | 8v5k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8v5k_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8v5k_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8v5k_validation.xml.gz | 63.8 KB | Display | |
Data in CIF | 8v5k_validation.cif.gz | 96.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/v5/8v5k ftp://data.pdbj.org/pub/pdb/validation_reports/v5/8v5k | HTTPS FTP |
-Related structure data
Related structure data | 42983MC 8v62C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 55364.965 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: T1UCV5 #2: Antibody | Mass: 13726.373 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) #3: 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) #4: Sugar | Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Prefusion Human Respirovirus 3 Fusion Protein bound to Camelid nanobodies 4C03 and 4C06 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.277 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
Microscopy | Model: TFS GLACIOS |
---|---|
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: NONE |
---|---|
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 336418 / Symmetry type: POINT |