[English] 日本語
Yorodumi- PDB-7k25: Murine polyomavirus hexavalent capsomer, subparticle reconstruction -
+Open data
-Basic information
Entry | Database: PDB / ID: 7k25 | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | |||||||||||||||||||||
Components | Capsid protein VP1 | |||||||||||||||||||||
Keywords | VIRAL PROTEIN / polyomavirus / capsomer | |||||||||||||||||||||
Function / homology | Function and homology information caveolin-mediated endocytosis of virus by host cell / T=7 icosahedral viral capsid / host cell nucleus / virion attachment to host cell / structural molecule activity Similarity search - Function | |||||||||||||||||||||
Biological species | Mus musculus polyomavirus 1 | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
Authors | Goetschius, D.J. / Hafenstein, S.L. | |||||||||||||||||||||
Funding support | United States, 6items
| |||||||||||||||||||||
Citation | Journal: Elife / Year: 2020 Title: Antibody escape by polyomavirus capsid mutation facilitates neurovirulence. Authors: Matthew D Lauver / Daniel J Goetschius / Colleen S Netherby-Winslow / Katelyn N Ayers / Ge Jin / Daniel G Haas / Elizabeth L Frost / Sung Hyun Cho / Carol M Bator / Stephanie M Bywaters / ...Authors: Matthew D Lauver / Daniel J Goetschius / Colleen S Netherby-Winslow / Katelyn N Ayers / Ge Jin / Daniel G Haas / Elizabeth L Frost / Sung Hyun Cho / Carol M Bator / Stephanie M Bywaters / Neil D Christensen / Susan L Hafenstein / Aron E Lukacher / Abstract: JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. ...JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo-EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation. | |||||||||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7k25.cif.gz | 304.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7k25.ent.gz | 256.3 KB | Display | PDB format |
PDBx/mmJSON format | 7k25.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k2/7k25 ftp://data.pdbj.org/pub/pdb/validation_reports/k2/7k25 | HTTPS FTP |
---|
-Related structure data
Related structure data | 22643MC 7k22C 7k23C 7k24C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 42493.172 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus polyomavirus 1 / Production host: Mus musculoides (Temminck's mouse) / References: UniProt: A0A247D727, UniProt: P49302*PLUS |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Murine polyomavirus strain A2 / Type: VIRUS / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Murine polyomavirus strain A2 | ||||||||||||||||||||
Source (recombinant) | Organism: Mus musculus (house mouse) / Cell: NMuMG | ||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||
Virus shell | Diameter: 450 nm / Triangulation number (T number): 7 | ||||||||||||||||||||
Buffer solution | pH: 7.9 Details: 10 mM HEPES pH 7.9, 1 mM CaCl2, 1 mM MgCl2, 5 mM KCl | ||||||||||||||||||||
Buffer component |
| ||||||||||||||||||||
Specimen | Conc.: 2.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: MuPyV (2.8 mg/mL) | ||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Humidity: 95 % |
-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: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 929940 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL Details: Homology model for Fab was generated using SwissModel. Initial models were docked into density in Chimera. Fab CDR loops were manually rebuilt in Coot. Iterative rounds of real space ...Details: Homology model for Fab was generated using SwissModel. Initial models were docked into density in Chimera. Fab CDR loops were manually rebuilt in Coot. Iterative rounds of real space refinements (PHENIX) and manual adjustment (coot) were conducted to improve fit to density. | ||||||||||||||||||||||||||||||||
Atomic model building |
| ||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 27.23 Å2 | ||||||||||||||||||||||||||||||||
Refine LS restraints |
|