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- PDB-8j8n: Structure of p53 DNA-binding domain and ZNF568 KRAB domain complex -

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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 / 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 / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity ...negative regulation of helicase activity / 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 / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of cell cycle G2/M phase transition / oligodendrocyte apoptotic process / negative regulation of miRNA processing / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / mRNA transcription / bone marrow development / positive regulation of programmed necrotic cell death / circadian behavior / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / germ cell nucleus / RUNX3 regulates CDKN1A transcription / homolactic fermentation / 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 / regulation of DNA damage response, signal transduction by p53 class mediator / histone deacetylase regulator activity / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / mitochondrial DNA repair / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / thymocyte apoptotic process / B cell lineage commitment / TP53 Regulates Transcription of Caspase Activators and Caspases / entrainment of circadian clock by photoperiod / cardiac septum morphogenesis / negative regulation of mitophagy / negative regulation of DNA replication / Zygotic genome activation (ZGA) / positive regulation of release of cytochrome c from mitochondria / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / necroptotic process / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / negative regulation of telomere maintenance via telomerase / TFIID-class transcription factor complex binding / 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 by p53 class mediator / rRNA transcription / negative regulation of reactive oxygen species metabolic process / Transcriptional Regulation by VENTX / cellular response to UV-C / replicative senescence / general transcription initiation factor binding / cellular response to actinomycin D / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of RNA polymerase II transcription preinitiation complex assembly / neuroblast proliferation / viral process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of execution phase of apoptosis / Pyroptosis / hematopoietic stem cell differentiation / response to X-ray / embryonic organ development / chromosome organization / type II interferon-mediated signaling pathway / somitogenesis / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / hematopoietic progenitor cell differentiation / glial cell proliferation / negative regulation of fibroblast proliferation / positive regulation of cardiac muscle cell apoptotic process / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / cellular response to glucose starvation / mitophagy / cis-regulatory region sequence-specific DNA binding / positive regulation of intrinsic apoptotic signaling pathway / Regulation of TP53 Activity through Acetylation / gastrulation / response to salt stress / 14-3-3 protein binding / mitotic G1 DNA damage checkpoint signaling / negative regulation of proteolysis / cardiac muscle cell apoptotic process / MDM2/MDM4 family protein binding / transcription repressor complex / intrinsic apoptotic signaling pathway
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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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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

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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

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Experimental details

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Experiment

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

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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

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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)

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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

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