+Open data
-Basic information
Entry | Database: PDB / ID: 7ebz | ||||||
---|---|---|---|---|---|---|---|
Title | EV-D68 in complex with 2H12 Fab (state S1) | ||||||
Components |
| ||||||
Keywords | VIRUS / Enterovirus D68 / Monoclonal antibody / Uncoating | ||||||
Function / homology | Function and homology information picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / nucleoside-triphosphate phosphatase / protein complex oligomerization ...picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / symbiont-mediated suppression of host gene expression / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | ||||||
Biological species | Human enterovirus D68 Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.09 Å | ||||||
Authors | Xu, C. / Cong, Y. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2021 Title: Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Authors: Chao Zhang / Cong Xu / Wenlong Dai / Yifan Wang / Zhi Liu / Xueyang Zhang / Xuesong Wang / Haikun Wang / Sitang Gong / Yao Cong / Zhong Huang / Abstract: Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), ...Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ebz.cif.gz | 206.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7ebz.ent.gz | 167 KB | Display | PDB format |
PDBx/mmJSON format | 7ebz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ebz_validation.pdf.gz | 1005.7 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7ebz_full_validation.pdf.gz | 1017.8 KB | Display | |
Data in XML | 7ebz_validation.xml.gz | 34.1 KB | Display | |
Data in CIF | 7ebz_validation.cif.gz | 51.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eb/7ebz ftp://data.pdbj.org/pub/pdb/validation_reports/eb/7ebz | HTTPS FTP |
-Related structure data
Related structure data | 31055MC 7ebrC 7ec5C 7ecyC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
| x 60
2 |
|
3 |
| x 5
4 |
| x 6
5 |
|
Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
-Capsid protein ... , 4 types, 4 molecules ACBD
#1: Protein | Mass: 32920.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Human enterovirus D68 / References: UniProt: A0A097BW12 |
---|---|
#2: Protein | Mass: 27112.814 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Human enterovirus D68 / References: UniProt: A0A097BW12 |
#3: Protein | Mass: 27567.135 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Human enterovirus D68 / References: UniProt: A0A097BW12 |
#4: Protein | Mass: 7336.960 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Human enterovirus D68 / References: UniProt: A0A097BW12 |
-Antibody , 2 types, 2 molecules EF
#5: Antibody | Mass: 22990.736 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
---|---|
#6: Antibody | Mass: 23582.920 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||
Buffer solution | pH: 7 | ||||||||||||||||||||||||
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 |
Image recording | Electron dose: 38 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.10.1_2155: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 3479 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|