+Open data
-Basic information
Entry | Database: PDB / ID: 6toq | ||||||
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Title | Crystal structure of a PP2A B56y/HTLV-1 integrase complex | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Phosphatase / integrase / complex / SLiM / dephosphorylation / cell signalling / motif mimicry | ||||||
Function / homology | Function and homology information protein phosphatase type 2A complex / protein phosphatase regulator activity / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated ...protein phosphatase type 2A complex / protein phosphatase regulator activity / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / Disassembly of the destruction complex and recruitment of AXIN to the membrane / CTLA4 inhibitory signaling / Platelet sensitization by LDL / protein phosphatase activator activity / chromosome, centromeric region / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / RHO GTPases Activate Formins / RAF activation / Degradation of beta-catenin by the destruction complex / DNA integration / Negative regulation of MAPK pathway / Separation of Sister Chromatids / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / Regulation of TP53 Degradation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA recombination / nucleic acid binding / negative regulation of cell population proliferation / Golgi apparatus / signal transduction / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Human T-cell leukemia virus type I Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.164 Å | ||||||
Authors | Minnell, J.J. / Barski, M.S. / Maertens, G.N. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Nat Commun / Year: 2020 Title: Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ. Authors: Michał S Barski / Jordan J Minnell / Zuzana Hodakova / Valerie E Pye / Andrea Nans / Peter Cherepanov / Goedele N Maertens / Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus and the most oncogenic pathogen. Many of the ~20 million HTLV-1 infected people will develop severe leukaemia or an ALS-like motor ...Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus and the most oncogenic pathogen. Many of the ~20 million HTLV-1 infected people will develop severe leukaemia or an ALS-like motor disease, unless a therapy becomes available. A key step in the establishment of infection is the integration of viral genetic material into the host genome, catalysed by the retroviral integrase (IN) enzyme. Here, we use X-ray crystallography and single-particle cryo-electron microscopy to determine the structure of the functional deltaretroviral IN assembled on viral DNA ends and bound to the B56γ subunit of its human host factor, protein phosphatase 2 A. The structure reveals a tetrameric IN assembly bound to two molecules of the phosphatase via a conserved short linear motif. Insight into the deltaretroviral intasome and its interaction with the host will be crucial for understanding the pattern of integration events in infected individuals and therefore bears important clinical implications. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6toq.cif.gz | 88 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6toq.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6toq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6toq_validation.pdf.gz | 429.6 KB | Display | wwPDB validaton report |
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Full document | 6toq_full_validation.pdf.gz | 442.3 KB | Display | |
Data in XML | 6toq_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | 6toq_validation.cif.gz | 21.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/to/6toq ftp://data.pdbj.org/pub/pdb/validation_reports/to/6toq | HTTPS FTP |
-Related structure data
Related structure data | 6qbtC 6qbvC 6qbwC 6tjuC 7pelC 2jakS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 11171.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human T-cell leukemia virus type I / Gene: pol / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 / Variant (production host): DE3 / References: UniProt: A0A1Y1CAL3 |
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#2: Protein | Mass: 43301.129 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PPP2R5C, KIAA0044 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 / Variant (production host): DE3 / References: UniProt: Q13362 |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.55 Å3/Da / Density % sol: 51.75 % / Description: Merged plates |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 6.2 Details: 0.1 M Na/KPO4 pH 6.2, 20-% 1,2-propanediol, 10% glycerol |
-Data collection
Diffraction | Mean temperature: 277 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9192 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 13, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9192 Å / Relative weight: 1 |
Reflection | Resolution: 3.16→80.29 Å / Num. obs: 10041 / % possible obs: 96.7 % / Redundancy: 1.4 % / CC1/2: 0.918 / Rmerge(I) obs: 0.167 / Rpim(I) all: 0.167 / Net I/σ(I): 3.3 |
Reflection shell | Resolution: 3.16→3.38 Å / Rmerge(I) obs: 0.489 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 1694 / CC1/2: 0.589 / % possible all: 94.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2JAK Resolution: 3.164→80.29 Å / Cor.coef. Fo:Fc: 0.921 / Cor.coef. Fo:Fc free: 0.873 / SU B: 27.25 / SU ML: 0.453 / Cross valid method: FREE R-VALUE / ESU R Free: 0.514 Details: Hydrogens have been added in their riding positions
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 57.582 Å2
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Refinement step | Cycle: LAST / Resolution: 3.164→80.29 Å
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Refine LS restraints |
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LS refinement shell |
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