+Open data
-Basic information
Entry | Database: PDB / ID: 7xzz | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the nucleosome in complex with p53 | |||||||||||||||||||||||||||||||||
Components |
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Keywords | GENE REGULATION/DNA / Transcription factor / Tumor-suppressor / GENE REGULATION-DNA COMPLEX | |||||||||||||||||||||||||||||||||
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 / regulation of tissue remodeling / glucose catabolic process to lactate via pyruvate / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / circadian behavior / bone marrow development / 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 / mitochondrial DNA repair / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / negative regulation of DNA replication / B cell lineage commitment / thymocyte apoptotic process / positive regulation of cardiac muscle cell 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 / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / positive regulation of release of cytochrome c from mitochondria / necroptotic process / Zygotic genome activation (ZGA) / positive regulation of execution phase of apoptosis / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / rRNA transcription / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / Transcriptional Regulation by VENTX / DNA damage response, signal transduction by p53 class mediator / replicative senescence / response to X-ray / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / mitophagy / negative regulation of tumor necrosis factor-mediated signaling pathway / cellular response to UV-C / positive regulation of RNA polymerase II transcription preinitiation complex assembly / hematopoietic stem cell differentiation / neuroblast proliferation / negative regulation of reactive oxygen species metabolic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / chromosome organization / T cell proliferation involved in immune response / negative regulation of megakaryocyte differentiation / Pyroptosis / embryonic organ development / glial cell proliferation / viral process / cis-regulatory region sequence-specific DNA binding / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / hematopoietic progenitor cell differentiation / protein localization to CENP-A containing chromatin / type II interferon-mediated signaling pathway / somitogenesis / cellular response to actinomycin D / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / core promoter sequence-specific DNA binding / cellular response to glucose starvation / negative regulation of stem cell proliferation / positive regulation of intrinsic apoptotic signaling pathway / Packaging Of Telomere Ends / negative regulation of fibroblast proliferation / Recognition and association of DNA glycosylase with site containing an affected purine Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.07 Å | |||||||||||||||||||||||||||||||||
Authors | Nishimura, M. / Nozawa, K. / Takizawa, Y. / Kurumizaka, H. | |||||||||||||||||||||||||||||||||
Funding support | Japan, 10items
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Citation | Journal: PNAS Nexus / Year: 2022 Title: Structural basis for p53 binding to its nucleosomal target DNA sequence. Authors: Masahiro Nishimura / Yoshimasa Takizawa / Kayo Nozawa / Hitoshi Kurumizaka / Abstract: The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome ...The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome remains elusive. Here we report the cryo-electron microscopy structures of the p53 DNA-binding domain and the full-length p53 protein complexed with a nucleosome containing the 20 base-pair target DNA sequence of p53 (p53BS). In the p53-nucleosome structures, the p53 DNA-binding domain forms a tetramer and specifically binds to the p53BS DNA, located near the entry/exit region of the nucleosome. The nucleosomal position of the p53BS DNA is within the genomic p21 promoter region. The p53 binding peels the DNA from the histone surface, and drastically changes the DNA path around the p53BS on the nucleosome. The C-terminal domain of p53 also binds to the DNA around the center and linker DNA regions of the nucleosome, as revealed by hydroxyl radical footprinting. These results provide important structural information for understanding the mechanism by which p53 binds the nucleosome and changes the chromatin structure for gene activation. | |||||||||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xzz.cif.gz | 456.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xzz.ent.gz | 350.8 KB | Display | PDB format |
PDBx/mmJSON format | 7xzz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xzz_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7xzz_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7xzz_validation.xml.gz | 61.3 KB | Display | |
Data in CIF | 7xzz_validation.cif.gz | 94.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xz/7xzz ftp://data.pdbj.org/pub/pdb/validation_reports/xz/7xzz | HTTPS FTP |
-Related structure data
Related structure data | 33535MC 7xzxC 7xzyC 7y00C 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
-Protein , 5 types, 12 molecules AEBFCGDHKLMN
#1: Protein | Mass: 15719.445 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H3C1 / Production host: Escherichia coli (E. coli) / References: UniProt: P68431 #2: Protein | Mass: 11676.703 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H4C1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62805 #3: Protein | Mass: 14447.825 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HIST1H2AE / Production host: Escherichia coli (E. coli) / References: UniProt: P04908 #4: Protein | Mass: 14217.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HIST1H2BJ / Production host: Escherichia coli (E. coli) / References: UniProt: P06899 #7: Protein | Mass: 43855.297 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TP53, P53 / Production host: Escherichia coli (E. coli) / References: UniProt: P04637 |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 52032.137 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA chain | Mass: 52312.316 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-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 |
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Molecular weight | Value: 0.398 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||
Source (recombinant) | Organism: Escherichia coli (E. coli) | ||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.25 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 289.15 K |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2739901 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.07 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92142 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||
Atomic model building |
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