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Title | Cryo-EM structure of the nucleosome in complex with p53 | |||||||||||||||||||||||||||||||||
![]() | Cryo-EM structure of the nucleosome in complex with p53 | |||||||||||||||||||||||||||||||||
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![]() | Transcription factor / Tumor-suppressor / GENE REGULATION-DNA COMPLEX | |||||||||||||||||||||||||||||||||
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 / negative regulation of DNA replication / ER overload response / 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 / TFIID-class transcription factor complex binding / rRNA transcription / mitophagy / SUMOylation of transcription factors / negative regulation of telomere maintenance via telomerase / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / Transcriptional Regulation by VENTX / response to X-ray / DNA damage response, signal transduction by p53 class mediator / replicative senescence / negative regulation of tumor necrosis factor-mediated signaling pathway / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / neuroblast proliferation / cellular response to UV-C / : / hematopoietic stem cell differentiation / negative regulation of reactive oxygen species metabolic process / chromosome organization / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / negative regulation of megakaryocyte differentiation / T cell proliferation involved in immune response / heterochromatin organization / glial cell proliferation / embryonic organ development / positive regulation of RNA polymerase II transcription preinitiation complex assembly / protein localization to CENP-A containing chromatin / Pyroptosis / cis-regulatory region sequence-specific DNA binding / hematopoietic progenitor cell differentiation / cellular response to glucose starvation / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / cellular response to actinomycin D / somitogenesis / CENP-A containing nucleosome / type II interferon-mediated signaling pathway / epigenetic regulation of gene expression / Packaging Of Telomere Ends / negative regulation of stem cell proliferation / core promoter sequence-specific DNA binding / positive regulation of intrinsic apoptotic signaling pathway Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.07 Å | |||||||||||||||||||||||||||||||||
![]() | Nishimura M / Nozawa K / Takizawa Y / Kurumizaka H | |||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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. | |||||||||||||||||||||||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26.7 KB 26.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10 KB | Display | ![]() |
Images | ![]() | 63.6 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 65.3 MB 65.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 799.5 KB | Display | ![]() |
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Full document | ![]() | 799 KB | Display | |
Data in XML | ![]() | 17 KB | Display | |
Data in CIF | ![]() | 22.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xzzMC ![]() 7xzxC ![]() 7xzyC ![]() 7y00C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Cryo-EM structure of the nucleosome in complex with p53 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33535_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_33535_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Cryo-EM structure of the nucleosome in complex with p53
+Supramolecule #1: Cryo-EM structure of the nucleosome in complex with p53
+Supramolecule #2: nucleosome, p53
+Supramolecule #3: DNA
+Macromolecule #1: Histone H3.1
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1-B/E
+Macromolecule #4: Histone H2B type 1-J
+Macromolecule #7: Cellular tumor antigen p53
+Macromolecule #5: DNA (169-MER)
+Macromolecule #6: DNA (169-MER)
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.25 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 289.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |