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Yorodumi- PDB-8dww: Chikungunya VLP in complex with neutralizing Fab 506.A08 (asymmet... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dww | |||||||||
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Title | Chikungunya VLP in complex with neutralizing Fab 506.A08 (asymmetric unit) | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / CSGID / Structural Genomics / Center for Structural Genomics of Infectious Diseases | |||||||||
Function / homology | Function and homology information togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / host cell plasma membrane ...togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / RNA binding / membrane Similarity search - Function | |||||||||
Biological species | Chikungunya virus strain Senegal 37997 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.13 Å | |||||||||
Authors | Adams, L.J. / Fremont, D.H. / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
Funding support | United States, 2items
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Citation | Journal: Sci Transl Med / Year: 2023 Title: A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans. Authors: Saravanan Raju / Lucas J Adams / James T Earnest / Kelly Warfield / Lo Vang / James E Crowe / Daved H Fremont / Michael S Diamond / Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle- ...Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle-adjuvanted vaccine (PXVX0317) from samples obtained from a phase 2 clinical trial in humans (NCT03483961). Immunization with PXVX0317 induced high levels of neutralizing antibody in serum against CHIKV and circulating antigen-specific B cells up to 6 months after immunization. Monoclonal antibodies (mAbs) generated from peripheral blood B cells of three PXVX0317-vaccinated individuals on day 57 after immunization potently neutralized CHIKV infection, and a subset of these inhibited multiple related arthritogenic alphaviruses. Epitope mapping and cryo-electron microscopy defined two broadly neutralizing mAbs that uniquely bind to the apex of the B domain of the E2 glycoprotein. These results demonstrate the inhibitory breadth and activity of the human B cell response induced by the PXVX0317 vaccine against CHIKV and potentially other related alphaviruses. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dww.cif.gz | 922.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dww.ent.gz | 760.5 KB | Display | PDB format |
PDBx/mmJSON format | 8dww.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dww_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8dww_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8dww_validation.xml.gz | 125.6 KB | Display | |
Data in CIF | 8dww_validation.cif.gz | 196.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dw/8dww ftp://data.pdbj.org/pub/pdb/validation_reports/dw/8dww | HTTPS FTP |
-Related structure data
Related structure data | 27763MC 8dwxC 8dwyC 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 , 3 types, 12 molecules BACDNMOPRQST
#1: Protein | Mass: 47346.715 Da / Num. of mol.: 4 / Fragment: UNP residues 810-1248 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chikungunya virus strain Senegal 37997 / Strain: 37997 / Production host: Homo sapiens (human) / References: UniProt: Q5XXP3 #4: Protein | Mass: 46858.312 Da / Num. of mol.: 4 / Fragment: UNP residues 330-748 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chikungunya virus strain Senegal 37997 / Strain: 37997 / Production host: Homo sapiens (human) / References: UniProt: Q5XXP3 #5: Protein | Mass: 16458.701 Da / Num. of mol.: 4 / Fragment: UNP residues 111-261 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chikungunya virus strain Senegal 37997 / Strain: 37997 / Production host: Homo sapiens (human) / References: UniProt: Q5XXP3 |
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-Antibody , 2 types, 8 molecules HVXZLUWY
#2: Antibody | Mass: 12963.226 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11483.660 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 1 types, 12 molecules
#6: 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: Chikungunya VLP in complex with neutralizing Fab 506.A08 (asymmetric unit) Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: Chikungunya virus strain Senegal 37997 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
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: 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: 59000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 38.25 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.13 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 704941 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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