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- EMDB-22643: Murine polyomavirus hexavalent capsomer, subparticle reconstruction -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22643 | |||||||||||||||||||||
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Title | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | |||||||||||||||||||||
![]() | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | |||||||||||||||||||||
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Function / homology | ![]() 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 | ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() | |||||||||||||||||||||
![]() | Goetschius DJ / Hafenstein SL | |||||||||||||||||||||
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
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 96.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 246.6 KB | ||
Others | ![]() ![]() | 79.8 MB 79.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7k25MC ![]() 7k22C ![]() 7k23C ![]() 7k24C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Murine polyomavirus hexavalent capsomer, subparticle reconstruction
File | emd_22643_half_map_1.map | ||||||||||||
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Annotation | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Murine polyomavirus hexavalent capsomer, subparticle reconstruction
File | emd_22643_half_map_2.map | ||||||||||||
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Annotation | Murine polyomavirus hexavalent capsomer, subparticle reconstruction | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Murine polyomavirus strain A2
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Murine polyomavirus strain A2
Supramolecule | Name: Murine polyomavirus strain A2 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 10636 / Sci species name: Murine polyomavirus strain A2 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No |
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Host system | Organism: ![]() ![]() ![]() |
Virus shell | Shell ID: 1 / Diameter: 450.0 Å / T number (triangulation number): 7 |
-Macromolecule #1: Capsid protein VP1
Macromolecule | Name: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 42.493172 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: APKRKSGVSK CETKCTKACP RPAPVPKLLI KGGMEVLDLV TGPDSVTEIE AFLNPRMGQP PTPESLTEGG QYYGWSRGIN LATSDTEDS PENNTLPTWS MAKLQLPMLN EDLTCDTLQM WEAVSVKTEV VGSGSLLDVH GFNKPTDTVN TKGISTPVEG S QYHVFAVG ...String: APKRKSGVSK CETKCTKACP RPAPVPKLLI KGGMEVLDLV TGPDSVTEIE AFLNPRMGQP PTPESLTEGG QYYGWSRGIN LATSDTEDS PENNTLPTWS MAKLQLPMLN EDLTCDTLQM WEAVSVKTEV VGSGSLLDVH GFNKPTDTVN TKGISTPVEG S QYHVFAVG GEPLDLQGLV TDARTKYKEE GVVTIKTITK KDMVNKDQVL NPISKAKLDK DGMYPVEIWH PDPAKNENTR YF GNYTGGT TTPPVLQFTN TLTTVLLDEN GVGPLCKGEG LYLSCVDIMG WRVTRNYDVH HWRGLPRYFK ITLRKRWVKN PYP MASLIS SLFNNMLPQV QGQPMEGENT QVEEVRVYDG TEPVPGDPDM TRYVDRFGKT KTVFPGN |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 2.8 mg/mL | ||||||||||
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Buffer | pH: 7.9 Component:
Details: 10 mM HEPES pH 7.9, 1 mM CaCl2, 1 mM MgCl2, 5 mM KCl | ||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % | ||||||||||
Details | MuPyV (2.8 mg/mL) |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 45.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | (PDB ID: , ) |
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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. |
Refinement | Space: REAL |
Output model | ![]() PDB-7k25: |