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- PDB-8u16: The ternary complex structure of DDB1-CRBN-SALL4(ZF1,2)-short bou... -

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Basic information

Entry
Database: PDB / ID: 8u16
TitleThe ternary complex structure of DDB1-CRBN-SALL4(ZF1,2)-short bound to Pomalidomide
Components
  • DNA damage-binding protein 1
  • Protein cereblon
  • Sal-like protein 4
KeywordsLIGASE / complex / glue
Function / homology
Function and homology information


POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / Transcriptional regulation of pluripotent stem cells / negative regulation of monoatomic ion transmembrane transport / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / embryonic limb morphogenesis / UV-damage excision repair / inner cell mass cell proliferation / ventricular septum development ...POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / Transcriptional regulation of pluripotent stem cells / negative regulation of monoatomic ion transmembrane transport / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / embryonic limb morphogenesis / UV-damage excision repair / inner cell mass cell proliferation / ventricular septum development / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4-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 / cullin family protein binding / viral release from host cell / somatic stem cell population maintenance / positive regulation of Wnt signaling pathway / ectopic germ cell programmed cell death / negative regulation of protein-containing complex assembly / positive regulation of viral genome replication / heterochromatin / proteasomal protein catabolic process / positive regulation of gluconeogenesis / Regulation of PTEN gene transcription / neural tube closure / nucleotide-excision repair / positive regulation of protein-containing complex assembly / Recognition of DNA damage by PCNA-containing replication complex / regulation of circadian rhythm / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Formation of Incision Complex in GG-NER / Wnt signaling pathway / 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 / site of double-strand break / Neddylation / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / Potential therapeutics for SARS / proteasome-mediated ubiquitin-dependent protein catabolic process / damaged DNA binding / transmembrane transporter binding / DNA-binding transcription factor activity, RNA polymerase II-specific / chromosome, telomeric region / protein ubiquitination / DNA repair / intracellular membrane-bounded organelle / apoptotic process / DNA damage response / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / protein-containing complex binding / nucleolus / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular space / DNA binding / extracellular exosome / zinc ion binding / nucleoplasm / metal ion binding / nucleus / membrane / cytoplasm / cytosol
Similarity search - Function
: / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon N-terminal domain profile. / Lon protease, N-terminal domain / Lon protease, N-terminal domain superfamily / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) ...: / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon N-terminal domain profile. / Lon protease, N-terminal domain / Lon protease, N-terminal domain superfamily / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / RSE1/DDB1/CPSF1 second beta-propeller / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / : / CPSF A subunit region / RSE1/DDB1/CPSF1 first beta-propeller / PUA-like superfamily / 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 / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
S-Pomalidomide / DNA damage-binding protein 1 / Protein cereblon / Sal-like protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsClifton, M.C. / Ma, X. / Ornelas, E.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Sci Rep / Year: 2023
Title: Structural and biophysical comparisons of the pomalidomide- and CC-220-induced interactions of SALL4 with cereblon.
Authors: Ma, X. / Leon, B. / Ornelas, E. / Dovala, D. / Tandeske, L. / Luu, C. / Pardee, G. / Widger, S. / Solomon, J.M. / Beckwith, R.E.J. / Moser, H. / Clifton, M.C. / Wartchow, C.A.
History
DepositionAug 30, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 27, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _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
A: Protein cereblon
B: DNA damage-binding protein 1
C: Sal-like protein 4
D: Protein cereblon
E: DNA damage-binding protein 1
F: Sal-like protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)286,47315
Polymers285,4726
Non-polymers1,0019
Water64936
1
A: Protein cereblon
B: DNA damage-binding protein 1
C: Sal-like protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)143,2067
Polymers142,7363
Non-polymers4694
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5240 Å2
ΔGint-41 kcal/mol
Surface area49550 Å2
MethodPISA
2
D: Protein cereblon
E: DNA damage-binding protein 1
F: Sal-like protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)143,2688
Polymers142,7363
Non-polymers5325
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5470 Å2
ΔGint-39 kcal/mol
Surface area49390 Å2
MethodPISA
Unit cell
Length a, b, c (Å)95.536, 151.986, 218.460
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

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Protein , 3 types, 6 molecules ADBECF

#1: Protein Protein cereblon


Mass: 42971.574 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96SW2
#2: Protein DNA damage-binding protein 1 / DDB p127 subunit / DNA damage-binding protein a / DDBa / Damage-specific DNA-binding protein 1 / ...DDB p127 subunit / DNA damage-binding protein a / DDBa / Damage-specific DNA-binding protein 1 / HBV X-associated protein 1 / XAP-1 / UV-damaged DNA-binding factor / UV-damaged DNA-binding protein 1 / UV-DDB 1 / XPE-binding factor / XPE-BF / Xeroderma pigmentosum group E-complementing protein / XPCe


Mass: 93347.078 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: residues 396 through 706 deleted, substituted with GNGNSG
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q16531
#3: Protein Sal-like protein 4 / Zinc finger protein 797 / Zinc finger protein SALL4


Mass: 6417.460 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SALL4, ZNF797 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UJQ4

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Non-polymers , 4 types, 45 molecules

#4: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Zn
#5: Chemical ChemComp-Y70 / S-Pomalidomide


Mass: 273.244 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C13H11N3O4 / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 36 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationY

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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: 2.78 Å3/Da / Density % sol: 55.72 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / Details: 0.2M Sodium malonate, 20% PEG 3350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 26, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.9→88.7 Å / Num. obs: 71316 / % possible obs: 100 % / Redundancy: 26.4 % / CC1/2: 0.995 / Rmerge(I) obs: 0.0773 / Rpim(I) all: 0.118 / Rrim(I) all: 0.609 / Rsym value: 0.9216 / Χ2: 1 / Net I/σ(I): 5 / Num. measured all: 1886081
Reflection shellResolution: 2.9→2.97 Å / % possible obs: 100 % / Redundancy: 25.2 % / Rmerge(I) obs: 8.198 / Num. measured all: 113305 / Num. unique obs: 4497 / CC1/2: 0.432 / Rpim(I) all: 1.66 / Rrim(I) all: 8.365 / Χ2: 1.04 / Net I/σ(I) obs: 0.6

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Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9→49.35 Å / SU ML: 0.45 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 34.3 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2727 3488 4.93 %
Rwork0.2191 --
obs0.2217 70742 99.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.9→49.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms18006 0 50 36 18092
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00918431
X-RAY DIFFRACTIONf_angle_d1.1525117
X-RAY DIFFRACTIONf_dihedral_angle_d6.0072567
X-RAY DIFFRACTIONf_chiral_restr0.0652955
X-RAY DIFFRACTIONf_plane_restr0.0093206
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.9-2.940.45631610.44132587X-RAY DIFFRACTION99
2.94-2.980.41361390.38222679X-RAY DIFFRACTION99
2.98-3.030.34571320.36292634X-RAY DIFFRACTION99
3.03-3.070.37191340.33372665X-RAY DIFFRACTION99
3.07-3.120.39841340.32272682X-RAY DIFFRACTION100
3.12-3.180.37171440.31862687X-RAY DIFFRACTION100
3.18-3.240.33411210.29792677X-RAY DIFFRACTION100
3.24-3.30.33271410.29812677X-RAY DIFFRACTION100
3.3-3.370.37781400.29052665X-RAY DIFFRACTION100
3.37-3.440.31361220.2822689X-RAY DIFFRACTION100
3.44-3.520.29231540.25082669X-RAY DIFFRACTION100
3.52-3.610.28981440.24652666X-RAY DIFFRACTION100
3.61-3.70.29621490.22362687X-RAY DIFFRACTION100
3.7-3.810.29681350.2172704X-RAY DIFFRACTION100
3.81-3.940.28051420.21552651X-RAY DIFFRACTION100
3.94-4.080.25961450.20532688X-RAY DIFFRACTION100
4.08-4.240.26471360.18742697X-RAY DIFFRACTION100
4.24-4.430.2291510.17022695X-RAY DIFFRACTION99
4.43-4.670.19751200.15452700X-RAY DIFFRACTION99
4.67-4.960.22951440.15632739X-RAY DIFFRACTION100
4.96-5.340.20851500.16922696X-RAY DIFFRACTION100
5.34-5.880.2411410.18872724X-RAY DIFFRACTION99
5.88-6.720.29851600.2012733X-RAY DIFFRACTION100
6.73-8.470.24761130.19712835X-RAY DIFFRACTION100
8.47-49.350.19491360.17692728X-RAY DIFFRACTION93
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.33642.8812-0.98694.7832-1.26253.1420.3047-0.43350.33241.1347-0.46130.4158-0.06130.1480.15250.63290.00140.01410.4618-0.1580.637457.800472.306835.8429
20.9540.54590.21087.2933-0.41050.6156-0.04310.27460.3325-0.7160.0006-0.83230.08150.20960.06690.52610.08830.03520.5974-0.01850.666649.203761.192514.664
32.249-0.6471-1.32382.97860.51491.8546-0.2911-0.3548-0.53960.11390.2487-0.22610.15810.12280.0560.65970.1825-0.12830.54480.05140.404550.620913.952538.5396
43.54490.3282-0.78523.6146-0.01723.449-0.1686-0.43770.05840.47010.2948-0.3484-0.11140.6133-0.11350.51990.0454-0.2830.6842-0.11140.526463.26124.273739.7843
53.43380.5194-0.09982.59391.32052.99040.06340.02120.1357-0.0517-0.0177-0.6388-0.07230.6144-0.08970.3470.0967-0.05340.59010.01270.713568.176818.824518.9535
62.8778-1.2861-0.40762.55830.12141.63880.01360.2155-0.1729-0.0901-0.12860.1735-0.0122-0.0060.11630.37640.0112-0.03030.3643-0.10060.263938.394916.372615.6247
72.6293-0.6007-0.2012.59880.20791.8791-0.0903-0.06850.11190.04310.01070.4129-0.3577-0.20260.07450.39490.1024-0.11120.3956-0.09090.428824.430341.327221.6227
81.7847-1.02380.42852.6690.11762.9278-0.2126-0.6162-0.12430.79950.07770.0986-0.0757-0.04730.12730.55770.088-0.0080.5663-0.01540.30336.425929.768344.9335
96.5315-0.46050.4336.32180.9338.8254-0.6566-0.9752-0.23370.96870.02640.7277-0.5139-0.65560.58270.7620.06280.02230.7858-0.00390.457529.869921.859760.0159
107.4882-3.2146-1.34539.1468-3.25064.87810.12230.53070.80721.7239-0.3342-0.1743-1.3435-1.04120.30850.94550.03830.0080.7249-0.10380.864258.992297.454227.9396
112.35353.0978-0.54967.70950.70721.1709-0.73720.49540.38770.01140.8752-0.779-0.36791.0663-0.10260.6403-0.07030.01631.0554-0.02621.514462.3059103.02423.958
128.0038-0.65013.394.9753-0.0716.7077-0.17950.80030.1332-0.71070.12910.0226-0.8780.9010.02150.7103-0.03750.01480.54730.07860.907349.839895.740316.5011
133.93833.59584.13545.30676.86249.045-0.1407-0.7866-0.1018-0.07260.0209-1.11650.52-0.69110.07910.88460.1295-0.28610.54460.11741.008743.516291.763122.9531
147.2298-2.26640.34036.54241.10135.14740.04280.1417-0.7842-0.6997-0.48870.3739-0.1119-0.19550.420.52460.0112-0.04830.38640.010.59969.99360.900873.2327
150.8076-1.58760.25246.1171-1.94110.8369-0.0459-0.18040.08270.1918-0.0142-0.2499-0.0943-0.09210.06720.3253-0.1192-0.06960.49670.09580.46541.316612.009394.65
162.14460.85960.93351.78840.84081.9578-0.06150.0410.2851-0.10760.0145-0.1499-0.16970.29380.04750.4226-0.10240.00880.47020.0680.537713.956354.465678.8241
176.41133.66451.38943.47040.80361.17140.0572-0.27450.84790.0018-0.44740.4185-0.4728-0.03130.3680.5078-0.10870.03310.5885-0.13660.7904-1.420963.010888.924
182.47040.7948-0.28543.553-0.17541.50080.1688-0.50660.30170.2151-0.30390.6586-0.0238-0.2610.14760.3764-0.0938-0.01680.5997-0.14150.6189-22.739238.566792.4557
191.47820.8627-0.52751.61630.09792.761-0.20790.45710.0861-0.6268-0.01770.21820.001-0.32420.19880.7144-0.0923-0.22380.64460.00740.4786-13.611242.571361.5993
209.2541-3.0223-2.34554.79280.36573.7538-0.67720.1617-0.1982-1.52360.904-1.80330.8794-0.6999-0.15211.0046-0.09740.18080.79620.02621.168312.6091-26.534383.1032
215.78981.7406-2.12575.30133.02443.578-0.4149-0.0753-0.6697-1.26210.75990.55220.3543-0.408-0.14960.6299-0.2194-0.20820.53660.17980.5769-0.5592-20.826690.0721
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 72 through 184 )
2X-RAY DIFFRACTION2chain 'A' and (resid 185 through 427 )
3X-RAY DIFFRACTION3chain 'B' and (resid 2 through 84 )
4X-RAY DIFFRACTION4chain 'B' and (resid 85 through 163 )
5X-RAY DIFFRACTION5chain 'B' and (resid 164 through 289 )
6X-RAY DIFFRACTION6chain 'B' and (resid 290 through 795 )
7X-RAY DIFFRACTION7chain 'B' and (resid 796 through 991 )
8X-RAY DIFFRACTION8chain 'B' and (resid 992 through 1097 )
9X-RAY DIFFRACTION9chain 'B' and (resid 1098 through 1140 )
10X-RAY DIFFRACTION10chain 'C' and (resid 380 through 393 )
11X-RAY DIFFRACTION11chain 'C' and (resid 394 through 404 )
12X-RAY DIFFRACTION12chain 'C' and (resid 405 through 421 )
13X-RAY DIFFRACTION13chain 'C' and (resid 422 through 432 )
14X-RAY DIFFRACTION14chain 'D' and (resid 72 through 184 )
15X-RAY DIFFRACTION15chain 'D' and (resid 185 through 427 )
16X-RAY DIFFRACTION16chain 'E' and (resid 2 through 289 )
17X-RAY DIFFRACTION17chain 'E' and (resid 290 through 385 )
18X-RAY DIFFRACTION18chain 'E' and (resid 386 through 963 )
19X-RAY DIFFRACTION19chain 'E' and (resid 964 through 1140 )
20X-RAY DIFFRACTION20chain 'F' and (resid 380 through 404 )
21X-RAY DIFFRACTION21chain 'F' and (resid 405 through 432 )

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