+Open data
-Basic information
Entry | Database: PDB / ID: 8uv3 | ||||||
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Title | Murine norovirus capsid protein + 1 mM MgCl2 | ||||||
Components | Capsid protein | ||||||
Keywords | VIRAL PROTEIN / norovirus / murine / activation | ||||||
Function / homology | Calicivirus coat protein C-terminal / Calicivirus coat protein C-terminal / Calicivirus coat protein / Calicivirus coat protein / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / virus-mediated perturbation of host defense response / Capsid protein Function and homology information | ||||||
Biological species | Murine norovirus 1 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.72 Å | ||||||
Authors | Smith, T.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Virol / Year: 2024 Title: The reversible activation of norovirus by metal ions. Authors: Michael Sherman / Faith Cox / Hong Smith / Mohamed H Habib / Stephanie Karst / Christiane E Wobus / Thomas J Smith / Abstract: Murine norovirus (MNV) undergoes extremely large conformational changes in response to the environment. The = 3 icosahedral capsid is composed of 180 copies of ~58-kDa VP1 comprised of N-terminus (N) ...Murine norovirus (MNV) undergoes extremely large conformational changes in response to the environment. The = 3 icosahedral capsid is composed of 180 copies of ~58-kDa VP1 comprised of N-terminus (N), shell (S), and C-terminal protruding (P) domains. At neutral pH, the P domains are loosely tethered to the shell and float ~15 Å above the surface. At low pH or in the presence of bile salts, the P domain drops onto the shell and this movement is accompanied by conformational changes within the P domain that enhance receptor interactions while blocking antibody binding. While previous crystallographic studies identified metal binding sites in the isolated P domain, the ~2.7-Å cryo-electron microscopy structures of MNV in the presence of Mg or Ca presented here show that metal ions can recapitulate the contraction observed at low pH or in the presence of bile. Further, we show that these conformational changes are reversed by dialysis against EDTA. As observed in the P domain crystal structures, metal ions bind to and contract the G'H' loop. This movement is correlated with the lifting of the C'D' loop and rotation of the P domain dimers about each other, exposing the bile salt binding pocket. Isothermal titration calorimetry experiments presented here demonstrate that the activation signals (bile salts, low pH, and metal ions) act in a synergistic manner that, individually, all result in the same activated structure. We present a model whereby these reversible conformational changes represent a uniquely dynamic and tissue-specific structural adaptation to the environment.IMPORTANCEThe highly mobile protruding domains on the calicivirus capsids are recognized by cell receptor(s) and antibodies. At neutral pH, they float ~15 Å above the shell but at low pH or in the presence of bile salts, they contract onto the surface. Concomitantly, changes within the P domain block antibody binding while enhancing receptor binding. While we previously demonstrated that metals also block antibody binding, it was unknown whether they might also cause similar conformational changes in the virion. Here, we present the near atomic cryo-electron microscopy structures of infectious murine norovirus (MNV) in the presence of calcium or magnesium ions. The metal ions reversibly induce the same P domain contraction as low pH and bile salts and act in a synergistic manner with the other stimuli. We propose that, unlike most other viruses, MNV facilely changes conformations as a unique means to escape immune surveillance as it moves through various tissues. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8uv3.cif.gz | 270.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8uv3.ent.gz | 217.6 KB | Display | PDB format |
PDBx/mmJSON format | 8uv3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uv3_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8uv3_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8uv3_validation.xml.gz | 56.9 KB | Display | |
Data in CIF | 8uv3_validation.cif.gz | 84.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uv/8uv3 ftp://data.pdbj.org/pub/pdb/validation_reports/uv/8uv3 | HTTPS FTP |
-Related structure data
Related structure data | 42604MC 8uuxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 56336.812 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Murine norovirus 1 / References: UniProt: Q2V8W4 #2: Chemical | #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Murine norovirus 1 / Type: VIRUS / Entity ID: #1 / Source: NATURAL |
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Source (natural) | Organism: Murine norovirus 1 |
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 48 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.72 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42721 / Symmetry type: POINT | ||||||||||||||||||||||||
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