[English] 日本語
Yorodumi
- PDB-9oty: DDB1-CRBN with CK1 alpha, SB-405483, and DEG-47: composite map an... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9oty
TitleDDB1-CRBN with CK1 alpha, SB-405483, and DEG-47: composite map and model submission
Components
  • Casein kinase I isoform alpha
  • DNA damage-binding protein 1
  • Protein cereblon
KeywordsLIGASE / E3 ligases / Cullin RING Ligase / CRL4 / Cereblon / CRBN / molecular glues / IMiDs
Function / homology
Function and homology information


intermediate filament cytoskeleton organization / Activation of SMO / negative regulation of monoatomic ion transmembrane transport / negative regulation of NLRP3 inflammasome complex assembly / cellular response to nutrient / beta-catenin destruction complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Beta-catenin phosphorylation cascade ...intermediate filament cytoskeleton organization / Activation of SMO / negative regulation of monoatomic ion transmembrane transport / negative regulation of NLRP3 inflammasome complex assembly / cellular response to nutrient / beta-catenin destruction complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / Disassembly of the destruction complex and recruitment of AXIN to the membrane / UV-damage excision repair / Maturation of nucleoprotein / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / limb development / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / positive regulation of Rho protein signal transduction / Cul4B-RING E3 ubiquitin ligase complex / Golgi organization / 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 / ectopic germ cell programmed cell death / positive regulation of Wnt signaling pathway / positive regulation of viral genome replication / negative regulation of protein-containing complex assembly / proteasomal protein catabolic process / sperm end piece / positive regulation of TORC1 signaling / positive regulation of gluconeogenesis / sperm principal piece / nucleotide-excision repair / positive regulation of protein-containing complex assembly / negative regulation of canonical Wnt signaling pathway / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / regulation of circadian rhythm / Degradation of beta-catenin by the destruction complex / kinetochore / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / spindle / 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 / sperm midpiece / rhythmic process / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / site of double-strand break / Neddylation / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / Potential therapeutics for SARS / proteasome-mediated ubiquitin-dependent protein catabolic process / damaged DNA binding / transmembrane transporter binding / protein phosphorylation / cell surface receptor signaling pathway / chromosome, telomeric region / protein kinase activity / non-specific serine/threonine protein kinase / cilium / nuclear speck / ciliary basal body / viral protein processing / protein ubiquitination / cell division / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / apoptotic process / DNA damage response / centrosome / negative regulation of apoptotic process / protein-containing complex binding / nucleolus / perinuclear region of cytoplasm / signal transduction / protein-containing complex / extracellular space
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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / : / Casein kinase I isoform alpha / DNA damage-binding protein 1 / Protein cereblon
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å
AuthorsRizvi, Z. / Lander, G.C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM143805 United States
CitationJournal: Nature / Year: 2026
Title: Identification of an allosteric site on the E3 ligase adapter cereblon.
Authors: Vanessa N Dippon / Zeba Rizvi / Anthony E Choudhry / Chun-Wa Chung / Ibrahim F Alkuraya / Wenqing Xu / Xavier B Tao / Anthony J Jurewicz / Jessica L Schneck / Wenqian Chen / Nicole M Curnutt ...Authors: Vanessa N Dippon / Zeba Rizvi / Anthony E Choudhry / Chun-Wa Chung / Ibrahim F Alkuraya / Wenqing Xu / Xavier B Tao / Anthony J Jurewicz / Jessica L Schneck / Wenqian Chen / Nicole M Curnutt / Farah Kabir / Kwok-Ho Chan / Markus A Queisser / Caterina Musetti / Han Dai / Gabriel C Lander / Andrew B Benowitz / Christina M Woo /
Abstract: Cereblon (CRBN) is the target of thalidomide derivatives that achieve therapeutic efficacy against some haematologic neoplasias by recruiting neosubstrates for degradation. Despite the intense ...Cereblon (CRBN) is the target of thalidomide derivatives that achieve therapeutic efficacy against some haematologic neoplasias by recruiting neosubstrates for degradation. Despite the intense investigation of orthosteric thalidomide derivatives, little is known about alternate binding sites on CRBN. Here we report an evolutionarily conserved cryptic allosteric binding site on CRBN. Small-molecule SB-405483 binds the allosteric site to cooperatively enhance the binding of orthosteric ligands and alter their neosubstrate degradation profiles. A survey of over 100 orthosteric ligands and their degradation targets reveals trends in the classes of compounds and neosubstrates in which degradation outcomes are enhanced or inhibited by SB-405483. Structural investigations provide a mechanistic basis for the effects of the allosteric ligand by shifting the conformational distribution of CRBN to a novel CRBN and increasing the CRBN state. The discovery of a cryptic allosteric binding site on CRBN that alters the functional effects of orthosteric ligands opens new directions with broad implications for improving the selectivity and efficacy of CRBN therapeutics.
History
DepositionMay 27, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 19, 2025Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Dec 24, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 1.1Dec 24, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 2.0Jan 21, 2026Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Refinement description / Structure summary
Category: atom_site / em_admin ...atom_site / em_admin / pdbx_contact_author / pdbx_struct_conn_angle / pdbx_struct_sheet_hbond / pdbx_validate_close_contact / pdbx_validate_polymer_linkage / pdbx_validate_rmsd_angle / pdbx_validate_torsion / refine / refine_ls_restr / struct_conf / struct_conn / struct_mon_prot_cis / struct_sheet / struct_sheet_order / struct_sheet_range
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _em_admin.last_update / _pdbx_struct_conn_angle.value / _pdbx_validate_polymer_linkage.dist / _struct_conn.pdbx_dist_value / _struct_mon_prot_cis.pdbx_omega_angle
Description: Model orientation/position
Details: In the earlier version, the two carbonyl groups of the glutarimide ring of DEG-47 were oriented toward the right within the Tri-Trp pocket. In the revised version, the ligand has been ...Details: In the earlier version, the two carbonyl groups of the glutarimide ring of DEG-47 were oriented toward the right within the Tri-Trp pocket. In the revised version, the ligand has been flipped such that these carbonyls now face toward the left within the Tri-Trp pocket.
Provider: author / Type: Coordinate replacement
Revision 1.2Jan 21, 2026Data content type: EM metadata / Data content type: EM metadata / Group: Experimental summary / Data content type: EM metadata / Category: em_admin / Data content type: EM metadata / Item: _em_admin.last_update
Revision 2.1Feb 4, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.pdbx_database_id_PubMed / _citation.title ..._citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name / _em_admin.last_update
Revision 1.3Feb 4, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.pdbx_database_id_PubMed / _citation.title ..._citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA damage-binding protein 1
B: Protein cereblon
C: Casein kinase I isoform alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)172,5126
Polymers171,7233
Non-polymers7893
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 3 types, 3 molecules ABC

#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: 93061.852 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Plasmid: pFASTBac / Cell line (production host): Sf9
Production host: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
References: UniProt: Q16531
#2: Protein Protein cereblon


Mass: 43978.617 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN, AD-006 / Plasmid: pFASTBac / Cell line (production host): Sf9
Production host: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
References: UniProt: Q96SW2
#3: Protein Casein kinase I isoform alpha / CKI-alpha / CK1


Mass: 34682.211 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CSNK1A1 / Plasmid: pFASTBac / Cell line (production host): Sf9
Production host: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
References: UniProt: P48729, non-specific serine/threonine protein kinase

-
Non-polymers , 3 types, 3 molecules

#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-A1CEH / N-{2-[(3R)-2,6-dioxopiperidin-3-yl]-1-oxo-2,3-dihydro-1H-isoindol-5-yl}benzamide


Mass: 363.367 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H17N3O4 / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-A1CEG / N-[3-(benzyloxy)pyridin-2-yl]-N'-(4-cyano-2-hydroxyphenyl)urea


Mass: 360.366 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H16N4O3 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: DDB1(BPB deleted)-CRBN complex with Casein kinase 1 alpha, SB-405483, and DEG-47
Type: COMPLEX
Details: The protein complex was incubated with CK1a, IMiD DEG-47, and allosteric binder SB-405483, and the mixture was incubated at 1:2:13:20 for 30 minutes and then frozen on 1.2/1.3 Au grids
Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightValue: 0.18366303 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
Strain: Sf9 / Plasmid: pFASTBac
Buffer solutionpH: 7 / Details: 10mM HEPES, 240mM NaCl, 3mM TCEP
Buffer component
IDConc.NameFormulaBuffer-ID
110 mMHEPESC8H18N2O4S1
2240 mMSodium ChlorideNaCl1
33 mMTCEPC9H15O6P1
SpecimenConc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: The protein complex was incubated with CK1a, IMiD DEG-47, and allosteric binder SB-405483, and the mixture was incubated at 1:2:13:20 for 30 minutes and then frozen on 1.2/1.3 Au grids
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277.15 K

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 190000 X / Calibrated magnification: 189189 X / Nominal defocus max: 1200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 77 K / Temperature (min): 70 K
Image recordingAverage exposure time: 4.08 sec. / Electron dose: 50 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 5691
Image scansSampling size: 15 µm / Width: 4096 / Height: 4096

-
Processing

EM software
IDNameVersionCategory
1cryoSPARC4.6.2particle selection
4cryoSPARC4.6.2CTF correction
7Coot0.9.8.95 ELmodel fitting
9cryoSPARC4.6.2initial Euler assignment
10cryoSPARC4.6.2final Euler assignment
12cryoSPARC4.6.23D reconstruction
13PHENIXv2.0orc1-5617model refinement
CTF correctionType: PHASE FLIPPING ONLY
Particle selectionNum. of particles selected: 3492611
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 328293 / Algorithm: FOURIER SPACE / Num. of class averages: 2 / Symmetry type: POINT
Atomic model buildingB value: 102.6 / Protocol: RIGID BODY FIT / Space: RECIPROCAL
Atomic model building

3D fitting-ID: 1 / Type: experimental model

IDPDB-IDPdb chain-IDChain-IDChain residue rangeDetailsSource nameAccession codeInitial refinement model-IDPdb chain residue range
1A1-1148The initial model was coming from crystal structure model from this study mentioned in citationOther
2B46-427The initial model was coming from crystal structure model from this study mentioned in citationOther
35fqd

5fqd

CC10-299CK1a model was taken from published structure 5fqdPDB5fqd210-299

+
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