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- PDB-9fzb: Human p53 DNA-binding domain bound to DARPin C10-H82R -

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Basic information

Entry
Database: PDB / ID: 9fzb
TitleHuman p53 DNA-binding domain bound to DARPin C10-H82R
Components
  • Cellular tumor antigen p53
  • DARPin C10-H82R
KeywordsDNA BINDING PROTEIN / p53 tumor suppressor / designed ankyrin repeat proteins (DARPins) / protein engineering / p53 reactivation in HPV-infected cells
Function / homology
Function and homology information


Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / negative regulation of helicase activity / 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 ...Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / negative regulation of helicase activity / 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 / regulation of fibroblast apoptotic process / intrinsic apoptotic signaling pathway in response to hypoxia / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / glucose catabolic process to lactate via pyruvate / positive regulation of mitochondrial membrane permeability / positive regulation of programmed necrotic cell death / negative regulation of mitophagy / mRNA transcription / circadian behavior / bone marrow development / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / regulation of DNA damage response, signal transduction by p53 class mediator / RUNX3 regulates CDKN1A transcription / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / : / histone deacetylase regulator activity / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / T cell lineage commitment / mitochondrial DNA repair / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / B cell lineage commitment / thymocyte apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / negative regulation of DNA replication / cardiac septum morphogenesis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / negative regulation of telomere maintenance via telomerase / necroptotic process / positive regulation of release of cytochrome c from mitochondria / Zygotic genome activation (ZGA) / Association of TriC/CCT with target proteins during biosynthesis / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / T cell proliferation involved in immune response / rRNA transcription / 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 / positive regulation of execution phase of apoptosis / Transcriptional Regulation by VENTX / general transcription initiation factor binding / replicative senescence / cellular response to actinomycin D / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / neuroblast proliferation / hematopoietic stem cell differentiation / positive regulation of RNA polymerase II transcription preinitiation complex assembly / response to X-ray / negative regulation of reactive oxygen species metabolic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / DNA damage response, signal transduction by p53 class mediator / chromosome organization / viral process / Pyroptosis / embryonic organ development / cis-regulatory region sequence-specific DNA binding / type II interferon-mediated signaling pathway / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / glial cell proliferation / hematopoietic progenitor cell differentiation / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / : / cellular response to glucose starvation / mitophagy / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of fibroblast proliferation / positive regulation of cardiac muscle cell apoptotic process / tumor necrosis factor-mediated signaling pathway / mitotic G1 DNA damage checkpoint signaling / Regulation of TP53 Activity through Acetylation / gastrulation / MDM2/MDM4 family protein binding / response to salt stress / 14-3-3 protein binding
Similarity search - Function
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 ...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
Similarity search - Domain/homology
Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.44 Å
AuthorsYuksel, B. / Balourdas, D.I. / Muenick, P. / Knapp, S. / Doetsch, V. / Joerger, A.C. / Structural Genomics Consortium (SGC)
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG)JO 1473/1-3 Germany
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2025
Title: DARPin-induced reactivation of p53 in HPV-positive cells.
Authors: Munick, P. / Strubel, A. / Balourdas, D.I. / Funk, J.S. / Mernberger, M. / Osterburg, C. / Dreier, B. / Schaefer, J.V. / Tuppi, M. / Yuksel, B. / Schafer, B. / Knapp, S. / Pluckthun, A. / ...Authors: Munick, P. / Strubel, A. / Balourdas, D.I. / Funk, J.S. / Mernberger, M. / Osterburg, C. / Dreier, B. / Schaefer, J.V. / Tuppi, M. / Yuksel, B. / Schafer, B. / Knapp, S. / Pluckthun, A. / Stiewe, T. / Joerger, A.C. / Dotsch, V.
History
DepositionJul 5, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 2, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Cellular tumor antigen p53
E: DARPin C10-H82R
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,5206
Polymers36,2682
Non-polymers2524
Water5,927329
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2210 Å2
ΔGint10 kcal/mol
Surface area14620 Å2
Unit cell
Length a, b, c (Å)37.713, 94.011, 53.170
Angle α, β, γ (deg.)90.000, 110.108, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

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Components

#1: Protein Cellular tumor antigen p53


Mass: 22721.775 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TP53 / Production host: Escherichia coli (E. coli) / References: UniProt: P04637
#2: Protein DARPin C10-H82R


Mass: 13546.318 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli)
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 329 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50.3 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: Protein solution: 2.6 mg/ml p53 DBD-DARPin C10-H82R complex in 50 mM HEPES, pH 7.5, 300 mM NaCl, 0.5 mM TCEP. Reservoir solution: 0.1 M Bis-Tris propane, pH 7.5, 0.02 M sodium potassium ...Details: Protein solution: 2.6 mg/ml p53 DBD-DARPin C10-H82R complex in 50 mM HEPES, pH 7.5, 300 mM NaCl, 0.5 mM TCEP. Reservoir solution: 0.1 M Bis-Tris propane, pH 7.5, 0.02 M sodium potassium phosphate, pH 7.5, 20% (w/v) PEG 3350, 10% (v/v) ethylene glycol. Drop volume ratio: 2:1

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 23, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.44→47 Å / Num. obs: 62097 / % possible obs: 98.9 % / Redundancy: 3.8 % / Biso Wilson estimate: 19.0208313695 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.045 / Rpim(I) all: 0.027 / Rrim(I) all: 0.053 / Net I/σ(I): 12.5
Reflection shellResolution: 1.44→1.47 Å / Redundancy: 3.9 % / Rmerge(I) obs: 0.612 / Mean I/σ(I) obs: 2 / Num. unique obs: 3110 / CC1/2: 0.825 / Rpim(I) all: 0.351 / Rrim(I) all: 0.707 / % possible all: 97.9

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Processing

Software
NameVersionClassification
PHENIX1.10.1_2155refinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.44→47 Å / SU ML: 0.147221909109 / Cross valid method: FREE R-VALUE / σ(F): 1.34347927413 / Phase error: 20.0406363028
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.183968942353 3019 4.86629378294 %
Rwork0.154445713844 59020 -
obs0.155892331052 62039 98.8055232604 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 27.4562657645 Å2
Refinement stepCycle: LAST / Resolution: 1.44→47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2442 0 13 329 2784
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.004899359901452551
X-RAY DIFFRACTIONf_angle_d0.7374277518793472
X-RAY DIFFRACTIONf_chiral_restr0.0776390417033391
X-RAY DIFFRACTIONf_plane_restr0.00489056704613462
X-RAY DIFFRACTIONf_dihedral_angle_d16.2978358942937
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.44-1.46250.2483950176781310.2162989199152635X-RAY DIFFRACTION97.5317348378
1.4625-1.48650.2492748786371470.2040308935052662X-RAY DIFFRACTION99.0130419457
1.4865-1.51210.2350206130311510.1935644871152636X-RAY DIFFRACTION97.1418612757
1.5121-1.53960.2181127998071670.1902303007012638X-RAY DIFFRACTION99.3623804463
1.5396-1.56920.2191914081631580.1809820389882661X-RAY DIFFRACTION97.9499652536
1.5692-1.60130.21229890561320.1682923207052632X-RAY DIFFRACTION99.1036213697
1.6013-1.63610.2227344457891310.1594607475542729X-RAY DIFFRACTION98.4170681349
1.6361-1.67420.2002580160171080.1490315210272689X-RAY DIFFRACTION99.1141034727
1.6742-1.7160.238294100943900.1526099260912743X-RAY DIFFRACTION98.3680555556
1.716-1.76240.2002262030871390.1492891416392645X-RAY DIFFRACTION99.5708154506
1.7624-1.81430.2057841566361350.1532763291142686X-RAY DIFFRACTION98.8091068301
1.8143-1.87280.1921049627611160.157361313282711X-RAY DIFFRACTION99.2277992278
1.8728-1.93980.1891288358161460.1686990454182665X-RAY DIFFRACTION99.0835389496
1.9398-2.01750.2106408965221080.1597337264492718X-RAY DIFFRACTION99.0883590463
2.0175-2.10930.1938954800161220.1663727970632733X-RAY DIFFRACTION98.9601386482
2.1093-2.22050.1977105775111440.1626007703332692X-RAY DIFFRACTION98.6778009743
2.2205-2.35960.2067708248641390.1575567637232676X-RAY DIFFRACTION99.0499648135
2.3596-2.54180.1822542196641920.1552054969462651X-RAY DIFFRACTION99.4751574528
2.5418-2.79750.177321671881290.153198069092701X-RAY DIFFRACTION99.1590749825
2.7975-3.20230.1832913050861640.1517750616382651X-RAY DIFFRACTION98.9107519325
3.2023-4.03420.1670555584781360.1426243988232714X-RAY DIFFRACTION98.8210818308
4.0342-470.1496831740231340.1429292015692752X-RAY DIFFRACTION98.9711934156

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