+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6791 | |||||||||
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Title | Cryo-EM structure of p300-p53 protein complex | |||||||||
Map data | Cryo-EM map of p300-p53 complex. p53 protein is a homotetrameric tumor suppresor. Transcriptional coactivator p300 is a multidomain protein with HAT (histone acetyltransferase) activity. | |||||||||
Sample |
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Keywords | transcription factor / autoacetylation / allosteric interaction / catalytically active form / TRANSCRIPTION | |||||||||
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 / thigmotaxis ...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 / thigmotaxis / histone H2B acetyltransferase activity / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / protein propionyltransferase activity / NOTCH2 intracellular domain regulates transcription / peptidyl-lysine acetylation / lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / histone H4 acetyltransferase activity / internal peptidyl-lysine acetylation / cellular response to L-leucine / histone H3 acetyltransferase activity / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / acetylation-dependent protein binding / Activation of the TFAP2 (AP-2) family of transcription factors / NGF-stimulated transcription / NFE2L2 regulating inflammation associated genes / TGFBR3 expression / STAT3 nuclear events downstream of ALK signaling / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / NFE2L2 regulating MDR associated enzymes / Polo-like kinase mediated events / regulation of androgen receptor signaling pathway / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of mitochondrion organization / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / regulation of fibroblast apoptotic process / positive regulation by host of viral transcription / 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 / 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 / circadian behavior / mRNA transcription / bone marrow development / face morphogenesis / Regulation of FOXO transcriptional activity by acetylation / regulation of mitochondrial membrane permeability involved in apoptotic process / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / regulation of glycolytic process / RUNX3 regulates NOTCH signaling / histone deacetylase regulator activity / germ cell nucleus / T cell lineage commitment / Regulation of gene expression by Hypoxia-inducible Factor / RUNX3 regulates CDKN1A transcription / Nuclear events mediated by NFE2L2 / regulation of DNA damage response, signal transduction by p53 class mediator / NOTCH4 Intracellular Domain Regulates Transcription / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / FOXO-mediated transcription of cell death genes / Regulation of NFE2L2 gene expression / megakaryocyte development / 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 / TRAF6 mediated IRF7 activation / B cell lineage commitment / NFE2L2 regulating anti-oxidant/detoxification enzymes / thymocyte apoptotic process / peptide-lysine-N-acetyltransferase activity / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / NFE2L2 regulating tumorigenic genes / Regulation of TP53 Activity through Association with Co-factors / macrophage derived foam cell differentiation / regulation of tubulin deacetylation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | 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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_6791.map.gz | 7.4 MB | EMDB map data format | |
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Header (meta data) | emd-6791-v30.xml emd-6791.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_6791_fsc.xml | 5.4 KB | Display | FSC data file |
Images | emd_6791.png | 153.5 KB | ||
Filedesc metadata | emd-6791.cif.gz | 6.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6791 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6791 | HTTPS FTP |
-Validation report
Summary document | emd_6791_validation.pdf.gz | 507.9 KB | Display | EMDB validaton report |
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Full document | emd_6791_full_validation.pdf.gz | 507.4 KB | Display | |
Data in XML | emd_6791_validation.xml.gz | 8.4 KB | Display | |
Data in CIF | emd_6791_validation.cif.gz | 10.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6791 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6791 | HTTPS FTP |
-Related structure data
Related structure data | 5xzcMC 6792C 6k4nC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_6791.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM map of p300-p53 complex. p53 protein is a homotetrameric tumor suppresor. Transcriptional coactivator p300 is a multidomain protein with HAT (histone acetyltransferase) activity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.89 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : p300-p53 complex
Entire | Name: p300-p53 complex |
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Components |
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-Supramolecule #1: p300-p53 complex
Supramolecule | Name: p300-p53 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Proteins were purified separately and then complex was made for cryo-EM. |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Histone acetyltransferase p300
Macromolecule | Name: Histone acetyltransferase p300 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: histone acetyltransferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 72.100062 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: KKIFKPEELR QALMPTLEAL YRQDPESLPF RQPVDPQLLG IPDYFDIVKS PMDLSTIKRK LDTGQYQEPW QYVDDIWLMF NNAWLYNRK TSRVYKYCSK LSEVFEQEID PVMQSLGYCC GRKLEFSPQT LCCYGKQLCT IPRDATYYSY QNRYHFCEKC F NEIQGESV ...String: KKIFKPEELR QALMPTLEAL YRQDPESLPF RQPVDPQLLG IPDYFDIVKS PMDLSTIKRK LDTGQYQEPW QYVDDIWLMF NNAWLYNRK TSRVYKYCSK LSEVFEQEID PVMQSLGYCC GRKLEFSPQT LCCYGKQLCT IPRDATYYSY QNRYHFCEKC F NEIQGESV SLGDDPSQPQ TTINKEQFSK RKNDTLDPEL FVECTECGRK MHQICVLHHE IIWPAGFVCD GCLKKSARTR KE NKFSAKR LPSTRLGTFL ENRVNDFLRR QNHPESGEVT VRVVHASDKT VEVKPGMKAR FVDSGEMAES FPYRTKALFA FEE IDGVDL CFFGMHVQEY GSDCPPPNQR RVYISYLDSV HFFRPKCLRT AVYHEILIGY LEYVKKLGYT TGHIWACPPS EGDD YIFHC HPPDQKIPKP KRLQEWYKKM LDKAVSERIV HDYKDIFKQA TEDRLTSAKE LPYFEGDFWP NVLEESIKEL EQEEE ERKR EENTSNESTD VTKGDSKNAK KKNNKKTSKN KSSLSRGNKK KPGMPNVSND LSQKLYATME KHKEVFFVIR LIAGPA ANS LPPIVDPDPL IPCDLMDGRD AFLTLARDKH LEFSSLRRAQ WSTMCMLVEL HTQSQD UniProtKB: Histone acetyltransferase p300 |
-Macromolecule #2: Cellular tumor antigen p53
Macromolecule | Name: Cellular tumor antigen p53 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 29.898908 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: PLSSSVPSQK TYQGSYGFRL GFLHSGTAKS VTCTYSPALN KMFCQLAKTC PVQLWVDSTP PPGTRVRAMA IYKQSQHMTE VVRRCPHHE RCSDSDGLAP PQHLIRVEGN LRVEYLDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS SCMGGMNRRP I LTIITLED ...String: PLSSSVPSQK TYQGSYGFRL GFLHSGTAKS VTCTYSPALN KMFCQLAKTC PVQLWVDSTP PPGTRVRAMA IYKQSQHMTE VVRRCPHHE RCSDSDGLAP PQHLIRVEGN LRVEYLDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS SCMGGMNRRP I LTIITLED SSGNLLGRNS FEVRVCACPG RDRRTEEENL RKKGEPHHEL PPGSTKRALP NNTSSSPQPK KKPLDGEYFT LQ IRGRERF EMFRELNEAL ELKDAQAG UniProtKB: Cellular tumor antigen p53 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | Film or detector model: FEI EAGLE (4k x 4k) / Average exposure time: 1.0 sec. / Average electron dose: 15.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 150.0 µm / Calibrated defocus max: 4.5 µm / Calibrated defocus min: 1.7 µm / Calibrated magnification: 78894 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal defocus max: 4.5 µm / Nominal defocus min: 1.7 µm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Residue range: 1046-1664 / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Output model | PDB-5xzc: |