+Open data
-Basic information
Entry | Database: PDB / ID: 6h0f | ||||||||||||
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Title | Structure of DDB1-CRBN-pomalidomide complex bound to IKZF1(ZF2) | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / E3 ubiquitin ligase / drug mediated protein-interaction / targeted protein degradation | ||||||||||||
Function / homology | Function and homology information negative regulation of monoatomic ion transmembrane transport / lymphocyte differentiation / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / NOTCH3 Intracellular Domain Regulates Transcription ...negative regulation of monoatomic ion transmembrane transport / lymphocyte differentiation / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / NOTCH3 Intracellular Domain Regulates Transcription / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / locomotory exploration behavior / mesoderm development / cullin family protein binding / viral release from host cell / positive regulation of Wnt signaling pathway / ectopic germ cell programmed cell death / proteasomal protein catabolic process / negative regulation of protein-containing complex assembly / positive regulation of viral genome replication / pericentric heterochromatin / positive regulation of gluconeogenesis / erythrocyte differentiation / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / positive regulation of protein-containing complex assembly / regulation of circadian rhythm / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Wnt signaling pathway / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / positive regulation of protein catabolic process / cellular response to UV / rhythmic process / chromatin organization / protein-macromolecule adaptor activity / Neddylation / site of double-strand break / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / transmembrane transporter binding / Potential therapeutics for SARS / chromosome, telomeric region / damaged DNA binding / protein ubiquitination / cell cycle / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein domain specific binding / DNA repair / negative regulation of DNA-templated transcription / apoptotic process / DNA damage response / protein-containing complex binding / nucleolus / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / perinuclear region of cytoplasm / protein-containing complex / DNA binding / extracellular space / extracellular exosome / nucleoplasm / identical protein binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.25 Å | ||||||||||||
Authors | Petzold, G. / Bunker, R.D. / Thoma, N.H. | ||||||||||||
Funding support | 3items
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Citation | Journal: Science / Year: 2018 Title: Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Authors: Sievers, Q.L. / Petzold, G. / Bunker, R.D. / Renneville, A. / Slabicki, M. / Liddicoat, B.J. / Abdulrahman, W. / Mikkelsen, T. / Ebert, B.L. / Thoma, N.H. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6h0f.cif.gz | 3.7 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6h0f.ent.gz | 3.1 MB | Display | PDB format |
PDBx/mmJSON format | 6h0f.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6h0f_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 6h0f_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 6h0f_validation.xml.gz | 154.1 KB | Display | |
Data in CIF | 6h0f_validation.cif.gz | 212 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h0/6h0f ftp://data.pdbj.org/pub/pdb/validation_reports/h0/6h0f | HTTPS FTP |
-Related structure data
Related structure data | 6h0gC 5fqdS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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4 |
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Unit cell |
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-Components
-Protein , 2 types, 8 molecules ADGJBEHK
#1: Protein | Mass: 95773.695 Da / Num. of mol.: 4 Mutation: Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG),Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG),Central WD40 ...Mutation: Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG),Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG),Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG),Central WD40 propeller domain (516-725 aa) replaced with a linker (sequence GNGNSG) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Trichoplusia ni cypovirus 15 / References: UniProt: Q16531*PLUS #2: Protein | Mass: 48976.117 Da / Num. of mol.: 4 / Mutation: N-terminally truncated (1-40 aa deleted) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN, AD-006 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q96SW2 |
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-Protein/peptide , 1 types, 4 molecules CFIL
#3: Protein/peptide | Mass: 4193.796 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IKZF1, IK1, IKAROS, LYF1, ZNFN1A1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q13422 |
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-Non-polymers , 3 types, 44 molecules
#4: Chemical | ChemComp-ZN / #5: Chemical | ChemComp-Y70 / #6: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.09 Å3/Da / Density % sol: 60.15 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion Details: Protein solution: 350 uM IKZF1-ZF2, 70 uM DDB1/CRBN, 80 uM pomalidomide in 50 mM HEPES pH 7.4, 200 mM NaCl, 0.25 mM TCEP Crystallisation solution: (Morpheus HT condition) 100 mM Morpheus ...Details: Protein solution: 350 uM IKZF1-ZF2, 70 uM DDB1/CRBN, 80 uM pomalidomide in 50 mM HEPES pH 7.4, 200 mM NaCl, 0.25 mM TCEP Crystallisation solution: (Morpheus HT condition) 100 mM Morpheus buffer system 1 pH 6.5, 10% (v/v) Morpheus NPS solution, 15% (v/v) ethylene glycol and 9.5% (w/v) poly(ethylene glycol) 5000 monomethyl ether. |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å | ||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Jan 30, 2017 | ||||||||||||||||||||||||
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 3.25→39.85 Å / Num. obs: 104192 / % possible obs: 94.4 % / Redundancy: 31.3 % / Biso Wilson estimate: 81.08 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.345 / Rpim(I) all: 0.061 / Rrim(I) all: 0.351 / Net I/σ(I): 11.5 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5FQD Resolution: 3.25→39.85 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.895 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.463
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Displacement parameters | Biso max: 299.98 Å2 / Biso mean: 97.73 Å2 / Biso min: 3.36 Å2
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Refine analyze | Luzzati coordinate error obs: 0.47 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.25→39.85 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.25→3.31 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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