[English] 日本語
Yorodumi
- PDB-9uum: Cryo-EM structure of mezigdomide-organized CRL4-DDB1-CRBN-IKZF3(Z... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9uum
TitleCryo-EM structure of mezigdomide-organized CRL4-DDB1-CRBN-IKZF3(ZF2-ZF3)-UbcH5a-Ub ubiquitylation assembly
Components
  • Cullin-4A
  • DNA damage-binding protein 1
  • E3 ubiquitin-protein ligase RBX1, N-terminally processed
  • NEDD8
  • Protein cereblon
  • Ubiquitin
  • Ubiquitin-conjugating enzyme E2 D1
  • Zinc finger protein Aiolos
KeywordsLIGASE / Molecular glue degrader / mezigdomide / CRL4 ubiquitin ligase / DDB1 / CRBN / Complex
Function / homology
Function and homology information


regulation of lymphocyte differentiation / regulation of B cell proliferation / regulation of B cell differentiation / positive regulation of protein polyubiquitination / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / negative regulation of granulocyte differentiation / Aberrant regulation of mitotic exit in cancer due to RB1 defects / negative regulation of monoatomic ion transmembrane transport ...regulation of lymphocyte differentiation / regulation of B cell proliferation / regulation of B cell differentiation / positive regulation of protein polyubiquitination / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / negative regulation of granulocyte differentiation / Aberrant regulation of mitotic exit in cancer due to RB1 defects / negative regulation of monoatomic ion transmembrane transport / Phosphorylation of the APC/C / Signaling by BMP / negative regulation of beige fat cell differentiation / cellular response to camptothecin / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / (E3-independent) E2 ubiquitin-conjugating enzyme / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / cellular response to chemical stress / regulation of DNA damage checkpoint / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / positive regulation by virus of viral protein levels in host cell / regulation of nucleotide-excision repair / RNA polymerase II transcription initiation surveillance / protein neddylation / spindle assembly involved in female meiosis / NEDD8 ligase activity / epigenetic programming in the zygotic pronuclei / protein K27-linked ubiquitination / negative regulation of response to oxidative stress / VCB complex / UV-damage excision repair / Cul5-RING ubiquitin ligase complex / E2 ubiquitin-conjugating enzyme / ubiquitin-ubiquitin ligase activity / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / SCF ubiquitin ligase complex / biological process involved in interaction with symbiont / Cul2-RING ubiquitin ligase complex / limb development / regulation of mitotic cell cycle phase transition / Cul3-RING ubiquitin ligase complex / negative regulation of type I interferon production / WD40-repeat domain binding / Formation of the ternary complex, and subsequently, the 43S complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4A-RING E3 ubiquitin ligase complex / Prolactin receptor signaling / negative regulation of mitophagy / Cul4-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / Regulation of APC/C activators between G1/S and early anaphase / mesoderm development / Ribosomal scanning and start codon recognition / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / Translation initiation complex formation / TGF-beta receptor signaling activates SMADs / ubiquitin conjugating enzyme activity / Transcriptional Regulation by VENTX / locomotory exploration behavior / hemopoiesis / regulation of proteolysis / T cell differentiation / somatic stem cell population maintenance / viral release from host cell / SARS-CoV-1 modulates host translation machinery / regulation of postsynapse assembly / Peptide chain elongation / negative regulation of BMP signaling pathway / cullin family protein binding / Selenocysteine synthesis / anatomical structure morphogenesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ectopic germ cell programmed cell death / Viral mRNA Translation / protein monoubiquitination / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of G1/S transition of mitotic cell cycle / GTP hydrolysis and joining of the 60S ribosomal subunit / positive regulation of Wnt signaling pathway / positive regulation of viral genome replication / L13a-mediated translational silencing of Ceruloplasmin expression / negative regulation of protein-containing complex assembly / Major pathway of rRNA processing in the nucleolus and cytosol / site of DNA damage / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / signal transduction in response to DNA damage / Nuclear events stimulated by ALK signaling in cancer / negative regulation of TORC1 signaling / protein K48-linked ubiquitination / transcription-coupled nucleotide-excision repair / negative regulation of insulin receptor signaling pathway / regulation of cellular response to insulin stimulus
Similarity search - Function
: / Nedd8-like ubiquitin / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / Lon N-terminal domain profile. / Lon protease, N-terminal domain ...: / Nedd8-like ubiquitin / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / 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) / : / Cullin, N-terminal / Cullin protein neddylation domain / Cullin, conserved site / Cullin alpha solenoid domain / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cullin / : / Cullin alpha+beta domain / Cullin homology domain / Cullin homology domain superfamily / Cullin family profile. / : / 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 / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / PUA-like superfamily / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Zinc finger, C2H2 type / Ubiquitin-conjugating enzyme/RWD-like / zinc finger / Zinc finger C2H2 type domain profile. / S27a-like superfamily / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Zinc finger C2H2 superfamily / Zinc finger C2H2 type domain signature. / Zinc finger C2H2-type / Zinc finger RING-type profile. / Zinc finger, RING-type / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Zinc-binding ribosomal protein / Zinc finger, RING/FYVE/PHD-type / Ubiquitin-like domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Mezigdomide / Ubiquitin-conjugating enzyme E2 D1 / E3 ubiquitin-protein ligase RBX1 / Ubiquitin-ribosomal protein eS31 fusion protein / Cullin-4A / Ubiquitin-like protein NEDD8 / DNA damage-binding protein 1 / Protein cereblon / Zinc finger protein Aiolos
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å
AuthorsDeng, Z.H. / Ai, H.S. / Liu, L.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)22137005, 92253302, 22227810, T2488301 China
CitationJournal: To Be Published
Title: Cryo-EM structure of mezigdomide-organized CRL4-DDB1-CRBN-IKZF3(ZF2-ZF3)-UbcH5a-Ub ubiquitylation assembly
Authors: Deng, Z.H. / Ai, H.S. / Liu, L.
History
DepositionMay 7, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jun 10, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Protein cereblon
D: Ubiquitin-conjugating enzyme E2 D1
I: Zinc finger protein Aiolos
N: NEDD8
U: Ubiquitin
R: E3 ubiquitin-protein ligase RBX1, N-terminally processed
B: DNA damage-binding protein 1
A: Cullin-4A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)318,95015
Polymers317,9898
Non-polymers9607
Water00
1


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

-
Components

-
Protein , 8 types, 8 molecules CDINURBA

#1: Protein Protein cereblon


Mass: 48874.941 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN, AD-006 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q96SW2
#2: Protein Ubiquitin-conjugating enzyme E2 D1 / (E3-independent) E2 ubiquitin-conjugating enzyme D1 / E2 ubiquitin-conjugating enzyme D1 / ...(E3-independent) E2 ubiquitin-conjugating enzyme D1 / E2 ubiquitin-conjugating enzyme D1 / Stimulator of Fe transport / SFT / UBC4/5 homolog / UbcH5 / Ubiquitin carrier protein D1 / Ubiquitin-conjugating enzyme E2(17)KB 1 / Ubiquitin-conjugating enzyme E2-17 kDa 1 / Ubiquitin-protein ligase D1


Mass: 16490.812 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UBE2D1, SFT, UBC5A, UBCH5, UBCH5A / Production host: Escherichia coli (E. coli)
References: UniProt: P51668, E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
#3: Protein Zinc finger protein Aiolos / Ikaros family zinc finger protein 3


Mass: 6549.474 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IKZF3, ZNFN1A3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UKT9
#4: Protein NEDD8 / Neddylin / Neural precursor cell expressed developmentally down-regulated protein 8 / NEDD-8 / ...Neddylin / Neural precursor cell expressed developmentally down-regulated protein 8 / NEDD-8 / Ubiquitin-like protein Nedd8


Mass: 8573.978 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NEDD8 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15843
#5: Protein Ubiquitin / Donor Ub


Mass: 8576.831 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RPS27A, UBA80, UBCEP1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62979
#6: Protein E3 ubiquitin-protein ligase RBX1, N-terminally processed / E3 ubiquitin-protein transferase RBX1 / N-terminally processed


Mass: 12457.076 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62877
#7: 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.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q16531
#8: Protein Cullin-4A / CUL-4A


Mass: 89368.867 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CUL4A / Production host: Escherichia coli (E. coli) / References: UniProt: Q13619

-
Non-polymers , 2 types, 7 molecules

#9: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#10: Chemical ChemComp-QFC / Mezigdomide


Mass: 567.610 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H30FN5O4 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Mezigdomide-organized CRL4-DDB1-CRBN-IKZF3(ZF2-ZF3)-UbcH5a-Ub ubiquitylation assembly
Type: COMPLEX / Entity ID: #1-#8 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
31Escherichia coli (E. coli)562
Buffer solutionpH: 7.8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

EM software
IDNameVersionCategory
1RELION3.1.1particle selection
2PHENIX1.21.1_5286model refinement
13cryoSPARC4.7.13D reconstruction
CTF correctionType: NONE
3D reconstructionResolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 172162 / Symmetry type: POINT
RefinementHighest resolution: 3.41 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00221218
ELECTRON MICROSCOPYf_angle_d0.53428704
ELECTRON MICROSCOPYf_dihedral_angle_d4.7642829
ELECTRON MICROSCOPYf_chiral_restr0.0453241
ELECTRON MICROSCOPYf_plane_restr0.0043679

+
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