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- PDB-7pel: CryoEM structure of simian T-cell lymphotropic virus intasome in ... -
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Basic information
Entry | Database: PDB / ID: 7pel | ||||||||||||||||||
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Title | CryoEM structure of simian T-cell lymphotropic virus intasome in complex with PP2A regulatory subunit B56 gamma | ||||||||||||||||||
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![]() | VIRAL PROTEIN / integrase / transferase / deltaretrovirus / PP2A / B56 / phosphatase / molecular mimicry / host factor / DNA-binding | ||||||||||||||||||
Function / homology | ![]() 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 / supercoiled DNA binding / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / CTLA4 inhibitory signaling / Platelet sensitization by LDL / 2-LTR circle formation / Formation of WDR5-containing histone-modifying complexes / Vpr-mediated nuclear import of PICs / protein phosphatase activator activity / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / mRNA 5'-splice site recognition / chromosome, centromeric region / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / heterochromatin / 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 / nuclear periphery / RHO GTPases Activate Formins / RAF activation / Degradation of beta-catenin by the destruction complex / euchromatin / DNA integration / RNA stem-loop binding / 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 / response to heat / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor binding / DNA recombination / response to oxidative stress / transcription coactivator activity / chromatin remodeling / negative regulation of cell population proliferation / chromatin binding / Golgi apparatus / signal transduction / positive regulation of transcription by RNA polymerase II / RNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() synthetic construct (others) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.34 Å | ||||||||||||||||||
![]() | Barski, M. / Pye, V.E. / Nans, A. / Cherepanov, P. / Maertens, G.N. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 358.5 KB | Display | ![]() |
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PDB format | ![]() | 273.5 KB | 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 | ![]() 11052 ![]() 6qbtC ![]() 6qbvC ![]() 6qbwC ![]() 6tjuC ![]() 6toqC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 33885.504 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 80394.680 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: fusion construct containing human LEDGF (residues 1-324 thus without the IBD domain) (gene PSIP1; O75475)) and human B56gammma (residues 11-380) regulatory subunit of PP2A (gene PPP2R5C) (no ...Details: fusion construct containing human LEDGF (residues 1-324 thus without the IBD domain) (gene PSIP1; O75475)) and human B56gammma (residues 11-380) regulatory subunit of PP2A (gene PPP2R5C) (no space for these details below),fusion construct containing human LEDGF (residues 1-324 thus without the IBD domain) (gene PSIP1; O75475)) and human B56gammma (residues 11-380) regulatory subunit of PP2A (gene PPP2R5C) (no space for these details below),fusion construct containing human LEDGF (residues 1-324 thus without the IBD domain) (gene PSIP1; O75475)) and human B56gammma (residues 11-380) regulatory subunit of PP2A (gene PPP2R5C) (no space for these details below),fusion construct containing human LEDGF (residues 1-324 thus without the IBD domain) (gene PSIP1; O75475)) and human B56gammma (residues 11-380) regulatory subunit of PP2A (gene PPP2R5C) (no space for these details below) Source: (gene. exp.) ![]() ![]() ![]() #3: DNA chain | Mass: 9221.909 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) #4: DNA chain | Mass: 8593.560 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) #5: Chemical | ChemComp-ZN / Has ligand of interest | N | |
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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 |
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Sample preparation
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Molecular weight | Value: 0.3311 MDa / Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 6 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.76 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Complex has been purified by SEC chromatography | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 295.15 K |
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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: 50.4 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18_3845: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4356108 Details: 2,198,454 (OH dataset) and 2,157,654 (GO dataset) 3D reconstructions using either separate subsets resulted in highly anisotropic maps due to severe preferential orientations. Because 3D-FCS ...Details: 2,198,454 (OH dataset) and 2,157,654 (GO dataset) 3D reconstructions using either separate subsets resulted in highly anisotropic maps due to severe preferential orientations. Because 3D-FCS analysis indicated favourable complementarity of the data, the datasets were merged as separate optic groups in Relion-3.1. 3D reconstruction, including Bayesian particle polishing, CTF and beam tilt refinement, as implemented in Relion-3.1, resulted in the final map with minimal anisotropy; 3D-FSC sphericity index of the final map was 0.967. | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.34 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 161921 Details: 3D reconstruction, including Bayesian particle polishing, CTF and beam tilt refinement, as implemented in Relion-3.1, resulted in the final map with minimal anisotropy; 3D-FSC sphericity ...Details: 3D reconstruction, including Bayesian particle polishing, CTF and beam tilt refinement, as implemented in Relion-3.1, resulted in the final map with minimal anisotropy; 3D-FSC sphericity index of the final map was 0.967. Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 31.31 / Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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Refine LS restraints |
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