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- PDB-7k24: Murine polyomavirus pentavalent capsomer, subparticle reconstruction -
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Open data
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Basic information
Entry | Database: PDB / ID: 7k24 | |||||||||||||||||||||
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Title | Murine polyomavirus pentavalent capsomer, subparticle reconstruction | |||||||||||||||||||||
![]() | Capsid protein VP1![]() | |||||||||||||||||||||
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Function / homology | ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||||||||
![]() | Goetschius, D.J. / Hafenstein, S.L. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 305.7 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22642MC ![]() 7k22C ![]() 7k23C ![]() 7k25C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | ![]() Mass: 42493.172 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Murine polyomavirus strain A2 / Type: VIRUS / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
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 |
Specimen | Conc.: 2.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
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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![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 |
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Processing
Software |
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EM software | Name: RELION / Version: 3.1 / Category: 3D reconstruction![]() | ||||||||||||||||||||||||
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 185988 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.56 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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