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- EMDB-36075: Structure of p53 DNA-binding domain and ZNF568 KRAB domain complex -

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Basic information

Entry
Database: EMDB / ID: EMD-36075
TitleStructure of p53 DNA-binding domain and ZNF568 KRAB domain complex
Map data
Sample
  • Complex: The complex of p53 DNA binding domain and ZNF568 KRAB domain
    • Protein or peptide: Zinc finger protein 568
    • Protein or peptide: Cellular tumor antigen p53
  • Ligand: ZINC ION
Keywordsp53 DBD / ZNF 568 KRAB / p53-dependent glycosis / mitochondrial respiration / PROTEIN BINDING
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 / DNA damage response, signal transduction by p53 class mediator / protein phosphatase 2A binding / transcription initiation-coupled chromatin remodeling / molecular function activator activity / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / cellular response to ionizing radiation / cellular response to xenobiotic stimulus / TP53 Regulates Metabolic Genes / TP53 Regulates Transcription of DNA Repair Genes / cellular response to gamma radiation / Regulation of NF-kappa B signaling / mRNA 3'-UTR binding / protein tetramerization / promoter-specific chromatin binding / Stabilization of p53 / molecular condensate scaffold activity / 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 / transcription coactivator binding / positive regulation of reactive oxygen species metabolic process / intracellular protein localization / histone deacetylase binding
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)
Methodsingle particle reconstruction / cryo EM / Resolution: 9.02 Å
AuthorsHan CW
Funding support Korea, Republic Of, 1 items
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, 2023-
Header (metadata) releaseMay 15, 2024-
Map releaseMay 15, 2024-
UpdateNov 27, 2024-
Current statusNov 27, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_36075.png

Downloads & links

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Map

FileDownload / File: emd_36075.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

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AxesZ (Sec.)Y (Row.)X (Col.)
0.76 Å/pix.
x 600 pix.
= 457.602 Å		0.76 Å/pix.
x 600 pix.
= 457.602 Å		0.76 Å/pix.
x 600 pix.
= 457.602 Å

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.76267 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.00676
Minimum - Maximum-0.052100703 - 0.13152245
Average (Standard dev.)0.000031953143 (±0.0044547287)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions600600600
Spacing600600600
CellA=B=C: 457.602 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_36075_additional_1.map
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Half map: #2

Fileemd_36075_half_map_1.map
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Half map: #1

Fileemd_36075_half_map_2.map
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Sample components

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Entire : The complex of p53 DNA binding domain and ZNF568 KRAB domain

EntireName: The complex of p53 DNA binding domain and ZNF568 KRAB domain
Components
  • Complex: The complex of p53 DNA binding domain and ZNF568 KRAB domain
    • Protein or peptide: Zinc finger protein 568
    • Protein or peptide: Cellular tumor antigen p53
  • Ligand: ZINC ION

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Supramolecule #1: The complex of p53 DNA binding domain and ZNF568 KRAB domain

SupramoleculeName: The complex of p53 DNA binding domain and ZNF568 KRAB domain
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 126 KDa

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Macromolecule #1: Zinc finger protein 568

MacromoleculeName: Zinc finger protein 568 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.940639 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MTSQSSVISN SCVTMERLSH MMERKAWCSQ ESALSEEEED TTRPLETVTF KDVAVDLTQE EWEQMKPAQR NLYRDVMLEN YSNLVTVGC QVTKPDVIFK LEQEEEPWVM EEEMFGRHCP

UniProtKB: Zinc finger protein 568

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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: 22.658805 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 RKK

UniProtKB: Cellular tumor antigen p53

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Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.8
GridModel: Quantifoil R2/2 / Material: GOLD / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 50 sec. / Details: 22mA
VitrificationCryogen name: NITROGEN

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 2.0 µm

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7w5q


Details: ZNF568 KRAB used PDB ID 7W5Q p53 DBD used PDB ID 7DVD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 9.02 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 76698
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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