+Open data
-Basic information
Entry | Database: PDB / ID: 5xzc | ||||||
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Title | Cryo-EM structure of p300-p53 protein complex | ||||||
Components |
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Keywords | TRANSCRIPTION / transcription factor / autoacetylation / allosteric interaction / catalytically active form | ||||||
Function / homology | Function and homology information behavioral defense response / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / swimming / peptide butyryltransferase activity / histone H2B acetyltransferase activity ...behavioral defense response / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / swimming / peptide butyryltransferase activity / histone H2B acetyltransferase activity / thigmotaxis / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / protein propionyltransferase activity / NOTCH2 intracellular domain regulates transcription / peptidyl-lysine acetylation / macrophage derived foam cell differentiation / lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / STAT family protein binding / histone H4 acetyltransferase activity / cellular response to L-leucine / internal peptidyl-lysine acetylation / histone H3 acetyltransferase activity / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / acetylation-dependent protein binding / NGF-stimulated transcription / STAT3 nuclear events downstream of ALK signaling / histone H3K18 acetyltransferase activity / Polo-like kinase mediated events / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / NFE2L2 regulates pentose phosphate pathway genes / NFE2L2 regulating MDR associated enzymes / regulation of androgen receptor signaling pathway / positive regulation of T-helper 17 cell lineage commitment / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of mitochondrion organization / positive regulation by host of viral transcription / 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 / face morphogenesis / circadian behavior / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Regulation of FOXO transcriptional activity by acetylation / RUNX3 regulates NOTCH signaling / Regulation of gene expression by Hypoxia-inducible Factor / regulation of glycolytic process / 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 / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / 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 / NOTCH3 Intracellular Domain Regulates Transcription / platelet formation / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / NFE2L2 regulating anti-oxidant/detoxification enzymes / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / megakaryocyte development / negative regulation of glial cell proliferation / peptide-lysine-N-acetyltransferase activity / FOXO-mediated transcription of cell death genes / negative regulation of neuroblast proliferation / regulation of tubulin deacetylation / Regulation of TP53 Activity through Association with Co-factors / nuclear androgen receptor binding / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 10.7 Å | ||||||
Authors | Ghosh, R. / Roy, S. / Sengupta, J. | ||||||
Citation | Journal: Biochemistry / Year: 2019 Title: Tumor Suppressor p53-Mediated Structural Reorganization of the Transcriptional Coactivator p300. Authors: Raka Ghosh / Stephanie Kaypee / Manidip Shasmal / Tapas K Kundu / Siddhartha Roy / Jayati Sengupta / Abstract: Transcriptional coactivator p300, a critical player in eukaryotic gene regulation, primarily functions as a histone acetyltransferase (HAT). It is also an important player in acetylation of a number ...Transcriptional coactivator p300, a critical player in eukaryotic gene regulation, primarily functions as a histone acetyltransferase (HAT). It is also an important player in acetylation of a number of nonhistone proteins, p53 being the most prominent one. Recruitment of p300 to p53 is pivotal in the regulation of p53-dependent genes. Emerging evidence suggests that p300 adopts an active conformation upon binding to the tetrameric p53, resulting in its enhanced acetylation activity. As a modular protein, p300 consists of multiple well-defined domains, where the structured domains are interlinked with unstructured linker regions. A crystal structure of the central domain of p300 encompassing Bromo, RING, PHD, and HAT domains demonstrates a compact module, where the HAT active site stays occluded by the RING domain. However, although p300 has a significant role in mediating the transcriptional activity of p53, only a few structural details on the complex of these two full-length proteins are available. Here, we present a cryo-electron microscopy (cryo-EM) study on the p300-p53 complex. The three-dimensional cryo-EM density map of the p300-p53 complex, when compared to the cryo-EM map of free p300, revealed that substantial change in the relative arrangement of Bromo and HAT domains occurs upon complex formation, which is likely required for exposing HAT active site and subsequent acetyltransferase activity. Our observation correlates well with previous studies showing that the presence of Bromodomain is obligatory for effective acetyltransferase activity of HAT. Thus, our result sheds new light on the mechanism whereby p300, following binding with p53, gets activated. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5xzc.cif.gz | 67.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5xzc.ent.gz | 37.3 KB | Display | PDB format |
PDBx/mmJSON format | 5xzc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5xzc_validation.pdf.gz | 815.1 KB | Display | wwPDB validaton report |
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Full document | 5xzc_full_validation.pdf.gz | 814.7 KB | Display | |
Data in XML | 5xzc_validation.xml.gz | 26.5 KB | Display | |
Data in CIF | 5xzc_validation.cif.gz | 38.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xz/5xzc ftp://data.pdbj.org/pub/pdb/validation_reports/xz/5xzc | HTTPS FTP |
-Related structure data
Related structure data | 6791MC 6792C 6k4nC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Details | One molecule of p300 interacts with four molecules of p53 (i.e, p300 monomer interacts with p53 tetramer) |
-Components
#1: Protein | Mass: 72100.062 Da / Num. of mol.: 1 / Fragment: UNP residues 1046-1664 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EP300, P300 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q09472, histone acetyltransferase |
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#2: Protein | Mass: 29898.908 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 |
-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: p300-p53 complex / Type: COMPLEX Details: Proteins were purified separately and then complex was made for cryo-EM. Entity ID: all / Source: MULTIPLE SOURCES | |||||||||||||||||||||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | 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: 279 K |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 59000 X / Calibrated magnification: 78894 X / Nominal defocus max: 4500 nm / Nominal defocus min: 1700 nm / Calibrated defocus min: 1700 nm / Calibrated defocus max: 4500 nm / Cs: 2 mm / C2 aperture diameter: 150 µm |
Specimen holder | Cryogen: NITROGEN Specimen holder model: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER |
Image recording | Average exposure time: 1 sec. / Electron dose: 15 e/Å2 / Film or detector model: FEI EAGLE (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 10.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10088 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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Atomic model building | Source name: PDB / Type: experimental model
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Refinement | Highest resolution: 10.7 Å |