[English] 日本語
Yorodumi- PDB-7cw3: Cryo-EM structure of Chikungunya virus in complex with mAb CHK-26... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7cw3 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Chikungunya virus in complex with mAb CHK-263 IgG (subregion around icosahedral 2-fold vertex) | ||||||
Components |
| ||||||
Keywords | VIRUS/IMMUNE SYSTEM / virus / IgG / localized reconstruction / VIRUS-IMMUNE SYSTEM complex | ||||||
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 / viral translational frameshifting / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell ...togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / symbiont entry into host cell / viral translational frameshifting / 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 / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Chikungunya virus Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 9.4 Å | ||||||
Authors | Zhou, Q.F. / Fox, J.M. / Earnest, J.T. / Ng, T.S. / Kim, A.S. / Fibriansah, G. / Kostyuchenko, V.A. / Shu, B. / Diamond, M.S. / Lok, S.M. | ||||||
Funding support | Singapore, 1items
| ||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2020 Title: Structural basis of Chikungunya virus inhibition by monoclonal antibodies. Authors: Qun Fei Zhou / Julie M Fox / James T Earnest / Thiam-Seng Ng / Arthur S Kim / Guntur Fibriansah / Victor A Kostyuchenko / Jian Shi / Bo Shu / Michael S Diamond / Shee-Mei Lok / Abstract: Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV ...Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral infection. CHK-124 aggregates virus particles and blocks attachment. Also, due to antibody-induced virus aggregation, fusion with endosomes and egress are inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus attachment and fusion. To determine the structural basis of neutralization, we generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that spans across E1 and E2 and locks the heterodimer together, likely preventing structural rearrangements required for fusion. These results provide structural insight as to how neutralizing antibody engagement of CHIKV inhibits different stages of the viral life cycle, which could inform vaccine and therapeutic design. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7cw3.cif.gz | 581.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7cw3.ent.gz | 383.5 KB | Display | PDB format |
PDBx/mmJSON format | 7cw3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7cw3_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7cw3_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7cw3_validation.xml.gz | 180.1 KB | Display | |
Data in CIF | 7cw3_validation.cif.gz | 291.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cw/7cw3 ftp://data.pdbj.org/pub/pdb/validation_reports/cw/7cw3 | HTTPS FTP |
-Related structure data
Related structure data | 30480MC 7cvyC 7cvzC 7cw0C 7cw2C C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 47503.016 Da / Num. of mol.: 18 / Source method: isolated from a natural source / Source: (natural) Chikungunya virus / References: UniProt: Q8JUX5*PLUS #2: Protein | Mass: 46904.559 Da / Num. of mol.: 18 / Source method: isolated from a natural source / Source: (natural) Chikungunya virus / References: UniProt: Q8JUX5*PLUS, togavirin #3: Antibody | Mass: 22872.670 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) #4: Antibody | Mass: 23381.570 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) #5: Protein | Mass: 16428.607 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Chikungunya virus References: UniProt: A0A6B9KBE1, UniProt: Q8JUX5*PLUS, togavirin Has protein modification | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight |
| ||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||
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 |
---|---|
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 / Cs: 2.7 mm |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 9.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 14693 / Symmetry type: POINT |