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Yorodumi- PDB-8r9w: PDCoV spike glycoprotein ectodomain in complex with the 22C10 ant... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8r9w | ||||||
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Title | PDCoV spike glycoprotein ectodomain in complex with the 22C10 antibody Fab fragment | ||||||
Components |
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Keywords | VIRAL PROTEIN / Spike / coronavirus / antibody / complex / PDCoV | ||||||
Function / homology | Function and homology information host cell membrane / endocytosis involved in viral entry into host cell / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion membrane / membrane Similarity search - Function | ||||||
Biological species | Deltacoronavirus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Debski-Antoniak, O. / Hurdiss, D.L. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Neutralizing antibodies reveal cryptic vulnerabilities and interdomain crosstalk in the porcine deltacoronavirus spike protein. Authors: Wenjuan Du / Oliver Debski-Antoniak / Dubravka Drabek / Rien van Haperen / Melissa van Dortmondt / Joline van der Lee / Ieva Drulyte / Frank J M van Kuppeveld / Frank Grosveld / Daniel L ...Authors: Wenjuan Du / Oliver Debski-Antoniak / Dubravka Drabek / Rien van Haperen / Melissa van Dortmondt / Joline van der Lee / Ieva Drulyte / Frank J M van Kuppeveld / Frank Grosveld / Daniel L Hurdiss / Berend-Jan Bosch / Abstract: Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus ...Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8r9w.cif.gz | 681 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8r9w.ent.gz | 540.6 KB | Display | PDB format |
PDBx/mmJSON format | 8r9w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r9/8r9w ftp://data.pdbj.org/pub/pdb/validation_reports/r9/8r9w | HTTPS FTP |
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-Related structure data
Related structure data | 19014MC 8r9xC 8r9yC 8r9zC 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
-Protein , 1 types, 3 molecules ABC
#1: Protein | Mass: 119212.852 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Deltacoronavirus / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: W8Q9Y7 |
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-Antibody , 2 types, 6 molecules HDELFG
#2: Antibody | Mass: 13107.698 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11553.769 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 48 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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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: PDCoV spike glycoprotein ectodomain in complex with the 22C10 antibody Fab fragment Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.52 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: 293F |
Buffer solution | pH: 7.8 |
Specimen | 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 / Humidity: 90 % |
-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: 1500 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
EM imaging optics | Energyfilter name: TFS Selectris |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 168789 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Cross-correlation coefficient / Details: Initial fitting was done using Chimera | ||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Accession code: 6BFU / Initial refinement model-ID: 1 / PDB-ID: 6BFU / Source name: PDB / Type: experimental model
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Refine LS restraints |
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