+Open data
-Basic information
Entry | Database: PDB / ID: 8ebp | ||||||
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Title | HMPV F dimer bound to RSV-199 Fab | ||||||
Components |
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Keywords | BIOSYNTHETIC PROTEIN / Human antibody / RSV and MPV fusion protein / complex cryo-EM structure / viral protein and antiviral protein | ||||||
Biological species | Human metapneumovirus A Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / Resolution: 3.38 Å | ||||||
Authors | Wen, X. / Jardetzky, T.S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Host Microbe / Year: 2023 Title: Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode. Authors: Xiaolin Wen / Naveenchandra Suryadevara / Nurgun Kose / Jing Liu / Xiaoyan Zhan / Laura S Handal / Lauren E Williamson / Andrew Trivette / Robert H Carnahan / Theodore S Jardetzky / James E Crowe / Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F ...Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ebp.cif.gz | 301.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ebp.ent.gz | 240.1 KB | Display | PDB format |
PDBx/mmJSON format | 8ebp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ebp_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8ebp_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8ebp_validation.xml.gz | 54.5 KB | Display | |
Data in CIF | 8ebp_validation.cif.gz | 81.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eb/8ebp ftp://data.pdbj.org/pub/pdb/validation_reports/eb/8ebp | HTTPS FTP |
-Related structure data
Related structure data | 27995MC 8dzwC 8e2uC 8eayC M: map data used to model this data C: citing same article (ref.) |
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-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 47513.301 Da / Num. of mol.: 2 / Mutation: Q100R, S101R, A113C, D185P, A339C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human metapneumovirus A / Production host: Homo sapiens (human) #2: Antibody | Mass: 22819.264 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 24022.906 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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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: MPV fusion protein complex with RSV-199 Fab / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Human metapneumovirus |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: NO |
-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: 81000 X / Nominal defocus max: 40000 nm / Nominal defocus min: 3451 nm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2774162 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 563257 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 4DAG Pdb chain-ID: A / Accession code: 4DAG / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refine LS restraints |
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