+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6792 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of p300 | |||||||||
Map data | Cryo-EM structure of p300. Transcriptional coactivator p300 is a large, multidomain protein that possess (HAT) histone acetyltransferase activity. | |||||||||
Sample |
| |||||||||
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 / regulation of mitochondrion organization / positive regulation by host of viral transcription / face morphogenesis / 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 / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / NOTCH3 Intracellular Domain Regulates Transcription / platelet formation / NFE2L2 regulating anti-oxidant/detoxification enzymes / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / megakaryocyte development / peptide-lysine-N-acetyltransferase activity / FOXO-mediated transcription of cell death genes / regulation of tubulin deacetylation / nuclear androgen receptor binding / acyltransferase activity / internal protein amino acid acetylation / protein acetylation / fat cell differentiation / positive regulation of transforming growth factor beta receptor signaling pathway / Formation of paraxial mesoderm / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / PI5P Regulates TP53 Acetylation / acetyltransferase activity / stimulatory C-type lectin receptor signaling pathway / Zygotic genome activation (ZGA) / RUNX3 regulates p14-ARF / NF-kappaB binding / histone acetyltransferase complex / Attenuation phase / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / cellular response to nutrient levels / negative regulation of protein-containing complex assembly / negative regulation of gluconeogenesis / somitogenesis / canonical NF-kappaB signal transduction / pre-mRNA intronic binding / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / regulation of cellular response to heat / histone acetyltransferase activity / skeletal muscle tissue development / histone acetyltransferase / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / Regulation of TP53 Activity through Acetylation / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / RORA activates gene expression / positive regulation of TORC1 signaling / transcription coregulator binding / CD209 (DC-SIGN) signaling / transcription initiation-coupled chromatin remodeling / negative regulation of autophagy / B cell differentiation / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / SUMOylation of transcription cofactors / lung development Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 9.8 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_6792.map.gz | 951.5 KB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-6792-v30.xml emd-6792.xml | 13.1 KB 13.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_6792_fsc.xml | 2.8 KB | Display | FSC data file |
Images | emd_6792.png | 122.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6792 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6792 | HTTPS FTP |
-Validation report
Summary document | emd_6792_validation.pdf.gz | 426.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_6792_full_validation.pdf.gz | 425.7 KB | Display | |
Data in XML | emd_6792_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_6792_validation.cif.gz | 7.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6792 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6792 | HTTPS FTP |
-Related structure data
Related structure data | 6k4nMC 6791C 5xzcC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_6792.map.gz / Format: CCP4 / Size: 1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM structure of p300. Transcriptional coactivator p300 is a large, multidomain protein that possess (HAT) histone acetyltransferase activity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.89 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : p300 protein
Entire | Name: p300 protein |
---|---|
Components |
|
-Supramolecule #1: p300 protein
Supramolecule | Name: p300 protein / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-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 |
---|---|
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 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 Component:
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI POLARA 300 |
---|---|
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: 1.5 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: 1.5 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 |