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Open data
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Basic information
Entry | Database: PDB / ID: 8f2h | ||||||||||||
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Title | Wild type P53 dimer structure from human cancer cells | ||||||||||||
![]() | Cellular tumor antigen p53 | ||||||||||||
![]() | ANTITUMOR PROTEIN / cancer / tumor suppressor / cell cycle / apoptosis / DNA repair | ||||||||||||
Function / homology | ![]() 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 / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / 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 / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair / T cell lineage commitment / ER overload response / negative regulation of DNA replication / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / positive regulation of execution phase of apoptosis / 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 / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription / TFIID-class transcription factor complex binding / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / mitophagy / Transcriptional Regulation by VENTX / DNA damage response, signal transduction by p53 class mediator / response to X-ray / replicative senescence / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / neuroblast proliferation / : / negative regulation of reactive oxygen species metabolic process / hematopoietic stem cell differentiation / chromosome organization / positive regulation of RNA polymerase II transcription preinitiation complex assembly / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / T cell proliferation involved in immune response / glial cell proliferation / Pyroptosis / cis-regulatory region sequence-specific DNA binding / embryonic organ development / hematopoietic progenitor cell differentiation / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to actinomycin D / somitogenesis / type II interferon-mediated signaling pathway / cellular response to glucose starvation / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / negative regulation of fibroblast proliferation / positive regulation of intrinsic apoptotic signaling pathway / gastrulation / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process / mitotic G1 DNA damage checkpoint signaling / 14-3-3 protein binding / Regulation of TP53 Activity through Acetylation / tumor necrosis factor-mediated signaling pathway / response to salt stress Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å | ||||||||||||
![]() | Solares, M. / Kelly, D.F. | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 251.8 KB | Display | ![]() |
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PDB format | ![]() | 201.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28816MC ![]() 8f2iC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 43711.176 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() |
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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
Component | Name: P53 dimer 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: ![]() |
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: Silicon nitride chips coated with Ni-NTA layers prior to sample application 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. |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / 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 |
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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: C2 (2 fold cyclic) | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8000 / Algorithm: BACK PROJECTION / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | B value: 50 / Protocol: FLEXIBLE FIT / Space: REAL | |||||||||||||||||||||||||||
Refine LS restraints |
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