[English] 日本語
Yorodumi
- EMDB-6791: Cryo-EM structure of p300-p53 protein complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-6791
TitleCryo-EM structure of p300-p53 protein complex
Map dataCryo-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
  • Complex: p300-p53 complex
    • Protein or peptide: Histone acetyltransferase p300
    • Protein or peptide: Cellular tumor antigen p53P53
Keywordstranscription factor / autoacetylation / allosteric interaction / catalytically active form / TRANSCRIPTION
Function / homology
Function and homology information


behavioral defense response / protein propionyltransferase activity / peptidyl-lysine propionylation / histone lactyltransferase activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / swimming / peptide butyryltransferase activity ...behavioral defense response / protein propionyltransferase activity / peptidyl-lysine propionylation / histone lactyltransferase 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 / NOTCH2 intracellular domain regulates transcription / lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / peptidyl-lysine acetylation / histone H3 acetyltransferase activity / histone H4 acetyltransferase activity / cellular response to L-leucine / internal peptidyl-lysine acetylation / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / acetylation-dependent protein binding / STAT3 nuclear events downstream of ALK signaling / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / NGF-stimulated transcription / histone H3K27 acetyltransferase activity / histone H3K18 acetyltransferase activity / Polo-like kinase mediated events / N-terminal peptidyl-lysine acetylation / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / regulation of androgen receptor signaling pathway / NFE2L2 regulating MDR associated enzymes / positive regulation by host of viral transcription / 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 / regulation of mitochondrion organization / 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 / face morphogenesis / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / mRNA transcription / bone marrow development / RUNX3 regulates NOTCH signaling / circadian behavior / histone deacetylase regulator activity / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of FOXO transcriptional activity by acetylation / germ cell nucleus / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / 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 / Regulation of NFE2L2 gene expression / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / NOTCH3 Intracellular Domain Regulates Transcription / regulation of glycolytic process / TRAF6 mediated IRF7 activation / negative regulation of neuroblast proliferation / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / platelet formation / megakaryocyte development / peptide-lysine-N-acetyltransferase activity / nuclear androgen receptor binding / NFE2L2 regulating anti-oxidant/detoxification enzymes / regulation of tubulin deacetylation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / macrophage derived foam cell differentiation / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / FOXO-mediated transcription of cell death genes / NFE2L2 regulating tumorigenic genes
Similarity search - Function
Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain ...Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain / CBP/p300-type histone acetyltransferase domain / CBP/p300, atypical RING domain superfamily / KIX domain / CREB-binding protein/p300, atypical RING domain / KIX domain profile. / CBP/p300-type histone acetyltransferase (HAT) domain profile. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily / p53-like transcription factor, DNA-binding / Nuclear receptor coactivator, interlocking / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Cellular tumor antigen p53 / Histone acetyltransferase p300
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 10.7 Å
AuthorsGhosh R / Roy S / Sengupta J
CitationJournal: 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
DepositionJul 12, 2017-
Header (metadata) releaseJan 23, 2019-
Map releaseJan 23, 2019-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 1.89
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 1.89
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-5xzc
  • Surface level: 1.89
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-5xzc
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_6791.png

Downloads & links

-
Map

FileDownload / File: emd_6791.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-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.
Voxel sizeX=Y=Z: 1.89 Å
Density
Contour LevelBy AUTHOR: 1.89 / Movie #1: 1.89
Minimum - Maximum-2.5380216 - 6.996958
Average (Standard dev.)0.1593592 (±0.7202969)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 241.92 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.891.891.89
M x/y/z128128128
origin x/y/z0.0000.0000.000
length x/y/z241.920241.920241.920
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS128128128
D min/max/mean-2.5386.9970.159

-
Supplemental data

-
Sample components

-
Entire : p300-p53 complex

EntireName: p300-p53 complex
Components
  • Complex: p300-p53 complex
    • Protein or peptide: Histone acetyltransferase p300
    • Protein or peptide: Cellular tumor antigen p53P53

-
Supramolecule #1: p300-p53 complex

SupramoleculeName: 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.
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Histone acetyltransferase p300

MacromoleculeName: 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 weightTheoretical: 72.100062 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: 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

MacromoleculeName: Cellular tumor antigen p53 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 29.898908 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: 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

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
Component:
ConcentrationNameFormula
10.0 mMTris-Cl
150.0 mMNaclSodium chloride
5.0 mMMgCl2
20.0 microMZnCl2
2.0 mMPMSF
1.0 mMDTT
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI POLARA 300
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 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 FIELDBright-field microscopy / Cs: 2.0 mm / Nominal defocus max: 4.5 µm / Nominal defocus min: 1.7 µm / Nominal magnification: 59000
Sample stageSpecimen holder model: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER
Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average exposure time: 1.0 sec. / Average electron dose: 15.0 e/Å2
Experimental equipment
Model: Tecnai Polara / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE / Details: Initial model was generate using EMAN2
Initial angle assignmentType: COMMON LINE / Software - Name: EMAN2 (ver. 2.12)
Final angle assignmentType: PROJECTION MATCHING / Software - Name: SPIDER
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 10.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: SPIDER / Number images used: 10088
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

4bhw


Chain - Chain ID: A / Chain - Residue range: 1046-1664 / Chain - Source name: PDB / Chain - Initial model type: experimental model
Output model

PDB-5xzc:
Cryo-EM structure of p300-p53 protein complex

-
Atomic model buiding 2

Initial model
PDB IDChain

3kmd

residue_range: 92-291, source_name: PDB, initial_model_type: experimental model

1c26

residue_range: 325-356, source_name: PDB, initial_model_type: experimental model
Output model

PDB-5xzc:
Cryo-EM structure of p300-p53 protein complex

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more