[English] 日本語
Yorodumi
- PDB-8j8n: Structure of p53 DNA-binding domain and ZNF568 KRAB domain complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8j8n
TitleStructure of p53 DNA-binding domain and ZNF568 KRAB domain complex
Components
  • Cellular tumor antigen p53
  • Zinc finger protein 568
KeywordsPROTEIN BINDING / p53 DBD / ZNF 568 KRAB / p53-dependent glycosis / mitochondrial respiration
Function / homology
Function and homology information


negative regulation of helicase activity / signal transduction by p53 class mediator / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of cell cycle G2/M phase transition / negative regulation of G1 to G0 transition / Transcriptional activation of cell cycle inhibitor p21 / negative regulation of pentose-phosphate shunt / Activation of NOXA and translocation to mitochondria / ATP-dependent DNA/DNA annealing activity ...negative regulation of helicase activity / signal transduction by p53 class mediator / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of cell cycle G2/M phase transition / negative regulation of G1 to G0 transition / Transcriptional activation of cell cycle inhibitor p21 / negative regulation of pentose-phosphate shunt / Activation of NOXA and translocation to mitochondria / ATP-dependent DNA/DNA annealing activity / oligodendrocyte apoptotic process / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / bone marrow development / cellular response to actinomycin D / circadian behavior / positive regulation of programmed necrotic cell death / RUNX3 regulates CDKN1A transcription / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / mRNA transcription / Regulation of TP53 Activity through Association with Co-factors / Urea cycle / ER overload response / hematopoietic stem cell differentiation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / TP53 Regulates Transcription of Caspase Activators and Caspases / intrinsic apoptotic signaling pathway by p53 class mediator / entrainment of circadian clock by photoperiod / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / PI5P Regulates TP53 Acetylation / positive regulation of release of cytochrome c from mitochondria / hematopoietic progenitor cell differentiation / Association of TriC/CCT with target proteins during biosynthesis / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Transcriptional Regulation by VENTX / TFIID-class transcription factor complex binding / replicative senescence / viral process / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / Pyroptosis / determination of adult lifespan / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / negative regulation of fibroblast proliferation / positive regulation of execution phase of apoptosis / type II interferon-mediated signaling pathway / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to glucose starvation / core promoter sequence-specific DNA binding / cis-regulatory region sequence-specific DNA binding / Regulation of TP53 Activity through Acetylation / intrinsic apoptotic signaling pathway / mitotic G1 DNA damage checkpoint signaling / positive regulation of intrinsic apoptotic signaling pathway / response to gamma radiation / 14-3-3 protein binding / MDM2/MDM4 family protein binding / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / protein phosphatase 2A binding / transcription initiation-coupled chromatin remodeling / Regulation of PTEN gene transcription / molecular function activator activity / tumor necrosis factor-mediated signaling pathway / cellular response to ionizing radiation / cellular response to xenobiotic stimulus / DNA damage response, signal transduction by p53 class mediator / TP53 Regulates Metabolic Genes / TP53 Regulates Transcription of DNA Repair Genes / Regulation of NF-kappa B signaling / mRNA 3'-UTR binding / protein tetramerization / promoter-specific chromatin binding / Stabilization of p53 / molecular condensate scaffold activity / cellular response to gamma radiation / negative regulation of cell growth / nucleotide-excision repair / G2/M Checkpoints / receptor tyrosine kinase binding / Autodegradation of the E3 ubiquitin ligase COP1 / cellular senescence / PML body / positive regulation of miRNA transcription / Oncogene Induced Senescence / DNA-binding transcription repressor activity, RNA polymerase II-specific / PKR-mediated signaling / Regulation of TP53 Activity through Methylation / G2/M DNA damage checkpoint / DNA Damage/Telomere Stress Induced Senescence / Pre-NOTCH Transcription and Translation / positive regulation of reactive oxygen species metabolic process / intracellular protein localization / histone deacetylase binding / autophagy
Similarity search - Function
: / Krueppel-associated box (KRAB) profile. / KRAB box / krueppel associated box / Krueppel-associated box / KRAB domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif ...: / Krueppel-associated box (KRAB) profile. / KRAB box / krueppel associated box / Krueppel-associated box / KRAB domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / : / 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 / Zinc finger, C2H2 type / zinc finger / Zinc finger C2H2 type domain profile. / Zinc finger C2H2 superfamily / Zinc finger C2H2 type domain signature. / Zinc finger C2H2-type
Similarity search - Domain/homology
Zinc finger protein 568 / Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 9.02 Å
AuthorsHan, C.W.
Funding support Korea, Republic Of, 1items
OrganizationGrant numberCountry
National Research Foundation (NRF, Korea)2021R1C1C2004755 Korea, Republic Of
CitationJournal: Int J Biol Macromol / Year: 2024
Title: Influence of the interaction between p53 and ZNF568 on mitochondrial oxidative phosphorylation.
Authors: Chang Woo Han / Mi Suk Jeong / Se Bok Jang /
Abstract: The tumor suppressor p53 plays important roles in suppressing the development and progression of cancer by responding to various stress signals. In addition, p53 can regulate the metabolic pathways ...The tumor suppressor p53 plays important roles in suppressing the development and progression of cancer by responding to various stress signals. In addition, p53 can regulate the metabolic pathways of cancer cells by regulating energy metabolism and oxidative phosphorylation. Here, we present a mechanism for the interaction between p53 and ZNF568. Initially, we used X-ray crystallography to determine the irregular loop structure of the ZNF568 KRAB domain; this loop plays an important role in the interaction between p53 and ZNF568. In addition, Cryo-EM was used to examine how the p53 DBD and ZNF568 KRAB domains bind together. The function of ZNF568 on p53-mediated mitochondrial respiration was confirmed by measuring glucose consumption and lactate production. These findings show that ZNF568 can reduce p53-mediated mitochondrial respiratory activity by binding to p53 and inhibiting the transcription of SCO2. SIGNIFICANCE: ZNF568 can directly bind to the p53 DBD and transcriptionally regulate the SCO2 gene. SCO2 transcriptional regulation by interaction between ZNF568 and p53 may regulate the balance between mitochondrial respiration and glycolysis.
History
DepositionMay 2, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 15, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 27, 2024Group: Data collection / Database references / Structure summary
Category: citation / citation_author ...citation / citation_author / em_admin / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
F: Zinc finger protein 568
A: Cellular tumor antigen p53
B: Cellular tumor antigen p53
C: Cellular tumor antigen p53
D: Cellular tumor antigen p53
E: Zinc finger protein 568
hetero molecules


Theoretical massNumber of molelcules
Total (without water)118,77810
Polymers118,5166
Non-polymers2624
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, The p53 DBD and ZNF568 KRAB complex particle. Chain E and F are ZNF KRAB domain. Chain A, B, C, and D are p53 DBD.
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Zinc finger protein 568


Mass: 13940.639 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ZNF568 / Production host: Escherichia coli (E. coli) / References: UniProt: C9JLX5
#2: Protein
Cellular tumor antigen p53 / Antigen NY-CO-13 / Phosphoprotein p53 / Tumor suppressor p53


Mass: 22658.805 Da / Num. of mol.: 4 / Fragment: DNA binding domain
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
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: The complex of p53 DNA binding domain and ZNF568 KRAB domain
Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Molecular weightValue: 0.126 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: 22mA / Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2
VitrificationCryogen name: NITROGEN

-
Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: DARK FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 2000 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k)

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.14_3260refinement
PHENIX1.14_3260refinement
CTF correctionDetails: ZNF568 KRAB used PDB ID 7W5Q p53 DBD used PDB ID 7DVD
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 9.02 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 76698 / Symmetry type: POINT
RefinementStereochemistry target values: CDL v1.2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00498234
ELECTRON MICROSCOPYf_angle_d0.98811156
ELECTRON MICROSCOPYf_chiral_restr0.05391220
ELECTRON MICROSCOPYf_plane_restr0.00791473
ELECTRON MICROSCOPYf_dihedral_angle_d19.22686202

+
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