[English] 日本語
Yorodumi
- PDB-7lps: Crystal structure of DDB1-CRBN-ALV1 complex bound to Helios (IKZF... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lps
TitleCrystal structure of DDB1-CRBN-ALV1 complex bound to Helios (IKZF2 ZF2)
Components
  • DNA damage-binding protein 1
  • Protein cereblon
  • Zinc finger protein Helios
KeywordsLIGASE / CRBN / DDB1 / IKZF2 / ALV / Degradation / E3 ligase
Function / homology
Function and homology information


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 / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex ...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 / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / 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 / viral release from host cell / cullin family protein binding / 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 / proteasomal protein catabolic process / positive regulation of gluconeogenesis / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / positive regulation of protein-containing complex assembly / regulation of circadian rhythm / DNA Damage Recognition in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / 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 / site of double-strand break / Neddylation / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / transmembrane transporter binding / Potential therapeutics for SARS / damaged DNA binding / chromosome, telomeric region / protein ubiquitination / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA repair / DNA damage response / protein-containing complex binding / negative regulation of apoptotic process / regulation of transcription by RNA polymerase II / nucleolus / apoptotic process / perinuclear region of cytoplasm / protein-containing complex / DNA binding / extracellular space / extracellular exosome / nucleoplasm / membrane / nucleus / metal ion binding / cytosol / cytoplasm
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) / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / : / CPSF A subunit region / 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
Chem-RN9 / DNA damage-binding protein 1 / Protein cereblon / Zinc finger protein Helios
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.78 Å
AuthorsNowak, R.P. / Fischer, E.S.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA214608 United States
Damon Runyon Cancer Research FoundationDRR-50-18 United States
CitationJournal: Nat.Chem.Biol. / Year: 2021
Title: Acute pharmacological degradation of Helios destabilizes regulatory T cells.
Authors: Wang, E.S. / Verano, A.L. / Nowak, R.P. / Yuan, J.C. / Donovan, K.A. / Eleuteri, N.A. / Yue, H. / Ngo, K.H. / Lizotte, P.H. / Gokhale, P.C. / Gray, N.S. / Fischer, E.S.
History
DepositionFeb 12, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 2, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 9, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA damage-binding protein 1
B: Protein cereblon
C: Zinc finger protein Helios
D: DNA damage-binding protein 1
E: Protein cereblon
F: Zinc finger protein Helios
G: DNA damage-binding protein 1
H: Protein cereblon
I: Zinc finger protein Helios
J: DNA damage-binding protein 1
K: Protein cereblon
L: Zinc finger protein Helios
hetero molecules


Theoretical massNumber of molelcules
Total (without water)703,33724
Polymers700,83412
Non-polymers2,50312
Water00
1
A: DNA damage-binding protein 1
B: Protein cereblon
C: Zinc finger protein Helios
hetero molecules


  • defined by author
  • Evidence: fluorescence resonance energy transfer, TR-FRET dimerization assay performed between CRBN-DDB1 and IKZF2 ZnF2 by titrating in ALV1. Dose dependent increase of signal indicating complex ...Evidence: fluorescence resonance energy transfer, TR-FRET dimerization assay performed between CRBN-DDB1 and IKZF2 ZnF2 by titrating in ALV1. Dose dependent increase of signal indicating complex formation was observed., gel filtration, Size exclusion chromatography of CRBN-DDB1 indicated monomeric form of the CRBN-DDB1 protein., gel filtration, Size exclusion chromatography of IKZF2 ZnF2 indicated monomeric form of the IKZF2 ZnF2 protein.
  • 176 kDa, 3 polymers
  • Search similar-shape structures of this assembly by Omokage search (details)
Theoretical massNumber of molelcules
Total (without water)175,8346
Polymers175,2093
Non-polymers6263
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
D: DNA damage-binding protein 1
E: Protein cereblon
F: Zinc finger protein Helios
hetero molecules


Theoretical massNumber of molelcules
Total (without water)175,8346
Polymers175,2093
Non-polymers6263
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
G: DNA damage-binding protein 1
H: Protein cereblon
I: Zinc finger protein Helios
hetero molecules


Theoretical massNumber of molelcules
Total (without water)175,8346
Polymers175,2093
Non-polymers6263
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
J: DNA damage-binding protein 1
K: Protein cereblon
L: Zinc finger protein Helios
hetero molecules


Theoretical massNumber of molelcules
Total (without water)175,8346
Polymers175,2093
Non-polymers6263
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)151.800, 117.292, 196.713
Angle α, β, γ (deg.)90.00, 97.30, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: 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: 127097.469 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q16531
#2: Protein
Protein cereblon


Mass: 44867.398 Da / Num. of mol.: 4
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
#3: Protein/peptide
Zinc finger protein Helios / Ikaros family zinc finger protein 2


Mass: 3243.704 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IKZF2, HELIOS, ZNFN1A2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UKS7
#4: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#5: Chemical
ChemComp-RN9 / 3-[3-[[1-[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]-2,5-bis(oxidanylidene)pyrrol-3-yl]amino]phenyl]-~{N}-(3-chloranyl-4-methyl-phenyl)propanamide


Mass: 494.927 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C25H23ClN4O5 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.37 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.57 / Details: 30% (w/v) PEG3350, 0.1 M Tris pH 8.57

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.9792 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Jul 12, 2019
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 3.78→150.57 Å / Num. obs: 67972 / % possible obs: 98.2 % / Redundancy: 4.6 % / Biso Wilson estimate: 82.75 Å2 / CC1/2: 0.988 / Rmerge(I) obs: 0.367 / Rpim(I) all: 0.286 / Net I/σ(I): 3.2
Reflection shellResolution: 3.78→3.86 Å / Redundancy: 4.5 % / Rmerge(I) obs: 1.813 / Mean I/σ(I) obs: 0.7 / Num. unique obs: 4033 / CC1/2: 0.28 / Rpim(I) all: 1.439 / % possible all: 87.6

-
Processing

Software
NameVersionClassification
BUSTER2.10.4 (11-DEC-2020)refinement
XDSVERSION Mar 15, 2019 BUILT=20190315data reduction
Aimless0.5.32data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5fqd

5fqd


Resolution: 3.78→150.57 Å / Cor.coef. Fo:Fc: 0.89 / Cor.coef. Fo:Fc free: 0.87 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.827
RfactorNum. reflection% reflectionSelection details
Rfree0.3031 3410 5.07 %RANDOM
Rwork0.2887 ---
obs0.2895 67299 97.6 %-
Displacement parametersBiso mean: 124.3 Å2
Baniso -1Baniso -2Baniso -3
1--2.5162 Å20 Å20.5111 Å2
2---3.1434 Å20 Å2
3---5.6596 Å2
Refine analyzeLuzzati coordinate error obs: 0.67 Å
Refinement stepCycle: LAST / Resolution: 3.78→150.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms37402 0 148 0 37550
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.00438294HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.751900HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d13312SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes6476HARMONIC5
X-RAY DIFFRACTIONt_it38142HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.01
X-RAY DIFFRACTIONt_other_torsion16.27
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion5048SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact24428SEMIHARMONIC4
LS refinement shellResolution: 3.78→3.82 Å / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.4572 -4.9 %
Rwork0.3808 1280 -
all0.3846 1346 -
obs--64.47 %
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)
10.6612-0.54090.14780.7704-0.11760.36520.1850.07410.11-0.0072-0.0547-0.08360.139-0.0452-0.13040.14420.056-0.097-0.05550.06630.281772.052112.0052-14.2263
20.1936-0.0094-0.23680.1983-0.04491.50460.0427-0.11130.011-0.16730.05370.1643-0.0920.0307-0.09640.20180.0511-0.13710.00140.00490.270564.412912.12126.3687
38.5025-2.7285-0.32838.14572.58451.5977-0.22990.14350.3505-0.5109-0.0072-0.29490.4991-0.53030.23710.170.1348-0.1691-0.1195-0.04240.262870.83119.162454.9437
40.02730.2035-0.134900.04840.44250.1987-0.121-0.0620.2397-0.2528-0.0812-0.1127-0.40990.05410.1642-0.1419-0.16140.3040.05060.197213.790446.071116.7248
51.24940.22360.120500.03241.12380.2165-0.20340.1116-0.1708-0.1055-0.04320.16160.0213-0.1110.12560.0551-0.14380.00610.16030.267624.669846.433-23.2006
60.0333.2568-0.13916.9591-2.51681.8907-0.14690.53530.0591-0.5685-0.05230.47580.50780.10480.19920.0960.0063-0.0642-0.07250.1540.290924.773156.5579-50.6647
70.75040.17530.08590.9995-0.20030.06440.1511-0.10190.06220.07050.0220.14220.03870.0571-0.17310.1762-0.09880.0142-0.1462-0.05120.3097-8.848710.6893111.9342
80.4843-0.0239-0.39140.41030.21251.50830.08780.08180.0039-0.01060.05390.07760.00980.0919-0.14170.1324-0.059-0.14150.02540.00830.2705-0.509110.800871.5421
97.24821.79712.53223.5782-2.70398.9820.0580.1408-0.4522-0.2310.01660.51910.5628-0.4557-0.07470.1416-0.1326-0.15370.1237-0.1610.1155-6.12098.603842.6348
101.03110.2370.10030.78820.44340.2644-0.08220.0999-0.0037-0.0380.0348-0.0614-0.0702-0.02690.04740.05850.0134-0.056-0.06170.02910.293648.616742.608981.784
110.5803-0.0628-0.27940.0006-0.11081.39910.0994-0.01290.02810.1-0.14770.07530.1878-0.04450.04840.227-0.0847-0.0419-0.1148-0.10220.294538.219945.5493121.4284
122.7229-3.2568-2.56158.31482.5168-0.70130.0638-0.54820.5046-0.4840.1478-0.5050.5968-0.0042-0.2116-0.0798-0.0129-0.07260.0706-0.15490.291737.759556.4469148.6659
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }
3X-RAY DIFFRACTION3{ C|* }
4X-RAY DIFFRACTION4{ D|* }
5X-RAY DIFFRACTION5{ E|* }
6X-RAY DIFFRACTION6{ F|* }
7X-RAY DIFFRACTION7{ G|* }
8X-RAY DIFFRACTION8{ H|* }
9X-RAY DIFFRACTION9{ I|* }
10X-RAY DIFFRACTION10{ J|* }
11X-RAY DIFFRACTION11{ K|* }
12X-RAY DIFFRACTION12{ L|* }

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more