+Open data
-Basic information
Entry | Database: PDB / ID: 8f2i | ||||||||||||
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Title | P53 monomer structure | ||||||||||||
Components | Cellular tumor antigen p53P53 | ||||||||||||
Keywords | ANTITUMOR PROTEIN / cancer / tumor suppressor / cell cycle / apoptosis / DNA repair | ||||||||||||
Function / homology | Function and homology information Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity ...Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / histone deacetylase regulator activity / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / germ cell nucleus / regulation of DNA damage response, signal transduction by p53 class mediator / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of glial cell proliferation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / mitochondrial DNA repair / T cell lineage commitment / positive regulation of execution phase of apoptosis / negative regulation of DNA replication / ER overload response / B cell lineage commitment / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / positive regulation of cardiac muscle cell apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / T cell proliferation involved in immune response / cardiac septum morphogenesis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / Zygotic genome activation (ZGA) / necroptotic process / rRNA transcription / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / mitophagy / SUMOylation of transcription factors / negative regulation of telomere maintenance via telomerase / general transcription initiation factor binding / intrinsic apoptotic signaling pathway by p53 class mediator / Transcriptional Regulation by VENTX / response to X-ray / DNA damage response, signal transduction by p53 class mediator / replicative senescence / chromosome organization / neuroblast proliferation / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / : / hematopoietic stem cell differentiation / negative regulation of reactive oxygen species metabolic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / glial cell proliferation / embryonic organ development / positive regulation of RNA polymerase II transcription preinitiation complex assembly / Pyroptosis / cis-regulatory region sequence-specific DNA binding / hematopoietic progenitor cell differentiation / cellular response to glucose starvation / cellular response to actinomycin D / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / type II interferon-mediated signaling pathway / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of stem cell proliferation / core promoter sequence-specific DNA binding / gastrulation / negative regulation of fibroblast proliferation / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process / transcription initiation-coupled chromatin remodeling / 14-3-3 protein binding / mitotic G1 DNA damage checkpoint signaling / Regulation of TP53 Activity through Acetylation / response to salt stress Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5 Å | ||||||||||||
Authors | Solares, M. / Kelly, D.F. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Chembiochem / Year: 2022 Title: High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials. Authors: Maria J Solares / G M Jonaid / William Y Luqiu / Samantha Berry / Janki Khadela / Yanping Liang / Madison C Evans / Kevin J Pridham / William J Dearnaley / Zhi Sheng / Deborah F Kelly / Abstract: Mutations in tumor suppressor genes, such as Tumor Protein 53 (TP53), are heavily implicated in aggressive cancers giving rise to gain- and loss-of-function phenotypes. While individual domains of ...Mutations in tumor suppressor genes, such as Tumor Protein 53 (TP53), are heavily implicated in aggressive cancers giving rise to gain- and loss-of-function phenotypes. While individual domains of the p53 protein have been studied extensively, structural information for full-length p53 remains incomplete. Functionalized microprocessor chips (microchips) with properties amenable to electron microscopy permitted us to visualize complete p53 assemblies for the first time. The new structures revealed p53 in an inactive dimeric state independent of DNA binding. Residues located at the protein-protein interface corresponded with modification sites in cancer-related hot spots. Changes in these regions may amplify the toxic effects of clinical mutations. Taken together, these results contribute advances in technology and imaging approaches to decode native protein models in different states of activation. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8f2i.cif.gz | 132.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f2i.ent.gz | 103.1 KB | Display | PDB format |
PDBx/mmJSON format | 8f2i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f2/8f2i ftp://data.pdbj.org/pub/pdb/validation_reports/f2/8f2i | HTTPS FTP |
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-Related structure data
Related structure data | 28817MC 8f2hC 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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-Components
#1: Protein | Mass: 43711.176 Da / Num. of mol.: 1 / Mutation: None / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: U87 MG cells / Organ: Brain tumor / Plasmid details: Glioblastoma / Variant: Wild-type / Tissue: Brain / References: UniProt: P04637 |
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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: P53 monomer isolated from U87-MG cells / Type: CELL / Details: Native protein, wild-type with no tags / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) / Cellular location: nucleus / Organ: Brain / Organelle: nucleus / Tissue: Brain tumor |
Buffer solution | pH: 7.5 Details: 20 mM HEPES (pH 7.5), 140 mM NaCl, 2 mM MgCl2, 2 mM CaCl2, 5 mM imidazole |
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Sample was placed on Silicon nitride chips coated with Ni-NTA layers |
Specimen support | Details: Cleaned microchips were coated with 25% Ni-NTA-containing lipid monolayers. Aliquots (2 microliters) of p53 fractions were added to the Ni-NTA-coated microchips and incubated for 2 minute at room temperature. Grid material: SILICON NITRIDE / Grid type: Homemade |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 298 K Details: The microchip samples were loaded into a FEI Mark III Vitrobot and flash-frozen into liquid ethane. |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
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Microscopy | Model: TFS TALOS F200C |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 142000 X / Nominal defocus max: 5000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: BASIC |
Specimen holder | Cryogen: NITROGEN Specimen holder model: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER |
Image recording | Average exposure time: 1 sec. / Electron dose: 5 e/Å2 / Film or detector model: FEI CETA (4k x 4k) / Num. of grids imaged: 10 / Num. of real images: 300 |
Image scans | Sampling size: 14 µm |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 8000 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8000 / Algorithm: BACK PROJECTION / Details: validated in Rmeasure / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | B value: 50 / Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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