[English] 日本語
Yorodumi
- EMDB-65569: Cryo-EM structure of DDB1-CRBN in complex with dHuR-2 and HuR -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-65569
TitleCryo-EM structure of DDB1-CRBN in complex with dHuR-2 and HuR
Map data
Sample
  • Complex: Ternary complex of HuR-CRBN/DDB1 with dHuR-2
    • Protein or peptide: DNA damage-binding protein 1
    • Protein or peptide: Protein cereblon
    • Protein or peptide: ELAV-like protein 1
  • Ligand: ZINC ION
  • Ligand: (3S)-3-[6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-1-benzofuran-3-yl]piperidine-2,6-dione
KeywordsMolecular glue degrader / Complex / RNA BINDING PROTEIN
Function / homology
Function and homology information


positive regulation of autophagosome size / lncRNA-mediated post-transcriptional gene silencing / negative regulation of miRNA-mediated gene silencing / HuR (ELAVL1) binds and stabilizes mRNA / regulation of stem cell population maintenance / negative regulation of monoatomic ion transmembrane transport / mRNA 3'-UTR AU-rich region binding / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei ...positive regulation of autophagosome size / lncRNA-mediated post-transcriptional gene silencing / negative regulation of miRNA-mediated gene silencing / HuR (ELAVL1) binds and stabilizes mRNA / regulation of stem cell population maintenance / negative regulation of monoatomic ion transmembrane transport / mRNA 3'-UTR AU-rich region binding / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / 3'-UTR-mediated mRNA stabilization / miRNA binding / mRNA stabilization / UV-damage excision repair / biological process involved in interaction with symbiont / limb development / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / mRNA destabilization / lncRNA 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 / sarcoplasm / viral release from host cell / cullin family protein binding / ectopic germ cell programmed cell death / response to glucose / positive regulation of viral genome replication / positive regulation of Wnt signaling pathway / negative regulation of protein-containing complex assembly / positive regulation of superoxide anion generation / proteasomal protein catabolic process / positive regulation of autophagy / positive regulation of gluconeogenesis / positive regulation of translation / nucleotide-excision repair / mRNA 3'-UTR binding / sperm end piece / P-body / positive regulation of protein-containing complex assembly / regulation of circadian rhythm / protein homooligomerization / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / Wnt signaling pathway / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Formation of Incision Complex in GG-NER / cytoplasmic stress granule / protein import into nucleus / Dual incision in TC-NER / positive regulation of protein catabolic process / Gap-filling DNA repair synthesis and ligation in TC-NER / cellular response to UV / rhythmic process / double-stranded RNA binding / site of double-strand break / sperm principal piece / Neddylation / cytoplasmic vesicle / sperm midpiece / Potential therapeutics for SARS / ubiquitin-dependent protein catabolic process / damaged DNA binding / transmembrane transporter binding / proteasome-mediated ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / chromosome, telomeric region / cell population proliferation / postsynapse / protein ubiquitination / ribonucleoprotein complex / DNA repair / mRNA binding / apoptotic process / DNA damage response / protein kinase binding / negative regulation of apoptotic process / protein-containing complex binding / nucleolus / perinuclear region of cytoplasm / glutamatergic synapse / endoplasmic reticulum / protein homodimerization activity / protein-containing complex / : / DNA binding / RNA binding / extracellular exosome / nucleoplasm / membrane / metal ion binding / nucleus / cytoplasm
Similarity search - Function
HuR, RNA recognition motif 2 / Splicing factor ELAV/Hu / Paraneoplastic encephalomyelitis antigen / 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 ...HuR, RNA recognition motif 2 / Splicing factor ELAV/Hu / Paraneoplastic encephalomyelitis antigen / 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 / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Nucleotide-binding alpha-beta plait domain superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
ELAV-like protein 1 / DNA damage-binding protein 1 / Protein cereblon
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsDou H / Zhu Y
Funding support China, 2 items
OrganizationGrant numberCountry
Other private2024 China
Ministry of Education (MoE, China)JYB2025XDXM502 China
CitationJournal: Nature / Year: 2026
Title: Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer.
Authors: Xiaocui Lu / Xiuyun Wang / Zheng Yang / Xusheng Wang / Lin Wang / Chunhui Xu / I-Chung Lo / Chenlu Geng / Lin Wang / Yisheng Pu / Keyu Zhang / Ziqiang Zhu / Lanxin Ye / Jiayuan Huang / ...Authors: Xiaocui Lu / Xiuyun Wang / Zheng Yang / Xusheng Wang / Lin Wang / Chunhui Xu / I-Chung Lo / Chenlu Geng / Lin Wang / Yisheng Pu / Keyu Zhang / Ziqiang Zhu / Lanxin Ye / Jiayuan Huang / Xiaofan Wei / Fang Bai / Yanan Zhu / Xiaobing Qian / Hao Dou / Hexiu Su / Yong Cang /
Abstract: BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF ...BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC.
History
DepositionJul 27, 2025-
Header (metadata) releaseApr 22, 2026-
Map releaseApr 22, 2026-
UpdateJun 24, 2026-
Current statusJun 24, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_65569.png

Downloads & links

-
Map

FileDownload / File: emd_65569.map.gz / Format: CCP4 / Size: 113.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 310 pix.
= 254.2 Å		0.82 Å/pix.
x 310 pix.
= 254.2 Å		0.82 Å/pix.
x 310 pix.
= 254.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.82 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0998
Minimum - Maximum-0.0016703934 - 2.4732497
Average (Standard dev.)0.0014821083 (±0.028299758)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions310310310
Spacing310310310
CellA=B=C: 254.2 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_65569_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_65569_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Ternary complex of HuR-CRBN/DDB1 with dHuR-2

EntireName: Ternary complex of HuR-CRBN/DDB1 with dHuR-2
Components
  • Complex: Ternary complex of HuR-CRBN/DDB1 with dHuR-2
    • Protein or peptide: DNA damage-binding protein 1
    • Protein or peptide: Protein cereblon
    • Protein or peptide: ELAV-like protein 1
  • Ligand: ZINC ION
  • Ligand: (3S)-3-[6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-1-benzofuran-3-yl]piperidine-2,6-dione

-
Supramolecule #1: Ternary complex of HuR-CRBN/DDB1 with dHuR-2

SupramoleculeName: Ternary complex of HuR-CRBN/DDB1 with dHuR-2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: DNA damage-binding protein 1

MacromoleculeName: DNA damage-binding protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 127.097469 KDa
Recombinant expressionOrganism: Insect cell expression vector pTIE1 (others)
SequenceString: MSYNYVVTAQ KPTAVNGCVT GHFTSAEDLN LLIAKNTRLE IYVVTAEGLR PVKEVGMYGK IAVMELFRPK GESKDLLFIL TAKYNACIL EYKQSGESID IITRAHGNVQ DRIGRPSETG IIGIIDPECR MIGLRLYDGL FKVIPLDRDN KELKAFNIRL E ELHVIDVK ...String:
MSYNYVVTAQ KPTAVNGCVT GHFTSAEDLN LLIAKNTRLE IYVVTAEGLR PVKEVGMYGK IAVMELFRPK GESKDLLFIL TAKYNACIL EYKQSGESID IITRAHGNVQ DRIGRPSETG IIGIIDPECR MIGLRLYDGL FKVIPLDRDN KELKAFNIRL E ELHVIDVK FLYGCQAPTI CFVYQDPQGR HVKTYEVSLR EKEFNKGPWK QENVEAEASM VIAVPEPFGG AIIIGQESIT YH NGDKYLA IAPPIIKQST IVCHNRVDPN GSRYLLGDME GRLFMLLLEK EEQMDGTVTL KDLRVELLGE TSIAECLTYL DNG VVFVGS RLGDSQLVKL NVDSNEQGSY VVAMETFTNL GPIVDMCVVD LERQGQGQLV TCSGAFKEGS LRIIRNGIGI HEHA SIDLP GIKGLWPLRS DPNRETDDTL VLSFVGQTRV LMLNGEEVEE TELMGFVDDQ QTFFCGNVAH QQLIQITSAS VRLVS QEPK ALVSEWKEPQ AKNISVASCN SSQVVVAVGR ALYYLQIHPQ ELRQISHTEM EHEVACLDIT PLGDSNGLSP LCAIGL WTD ISARILKLPS FELLHKEMLG GEIIPRSILM TTFESSHYLL CALGDGALFY FGLNIETGLL SDRKKVTLGT QPTVLRT FR SLSTTNVFAC SDRPTVIYSS NHKLVFSNVN LKEVNYMCPL NSDGYPDSLA LANNSTLTIG TIDEIQKLHI RTVPLYES P RKICYQEVSQ CFGVLSSRIE VQDTSGGTTA LRPSASTQAL SSSVSSSKLF SSSTAPHETS FGEEVEVHNL LIIDQHTFE VLHAHQFLQN EYALSLVSCK LGKDPNTYFI VGTAMVYPEE AEPKQGRIVV FQYSDGKLQT VAEKEVKGAV YSMVEFNGKL LASINSTVR LYEWTTEKEL RTECNHYNNI MALYLKTKGD FILVGDLMRS VLLLAYKPME GNFEEIARDF NPNWMSAVEI L DDDNFLGA ENAFNLFVCQ KDSAATTDEE RQHLQEVGLF HLGEFVNVFC HGSLVMQNLG ETSTPTQGSV LFGTVNGMIG LV TSLSESW YNLLLDMQNR LNKVIKSVGK IEHSFWRSFH TERKTEPATG FIDGDLIESF LDISRPKMQE VVANLQYDDG SGM KREATA DDLIKVVEEL TRIH

UniProtKB: DNA damage-binding protein 1

-
Macromolecule #2: Protein cereblon

MacromoleculeName: Protein cereblon / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.882449 KDa
Recombinant expressionOrganism: Insect cell expression vector pTIE1 (others)
SequenceString: NIINFDTSLP TSHTYLGADM EEFHGRTLHD DDSCQVIPVL PQVMMILIPG QTLPLQLFHP QEVSMVRNLI QKDRTFAVLA YSNVQEREA QFGTTAEIYA YREEQDFGIE IVKVKAIGRQ RFKVLELRTQ SDGIQQAKVQ ILPECVLPST MSAVQLESLN K CQIFPSKP ...String:
NIINFDTSLP TSHTYLGADM EEFHGRTLHD DDSCQVIPVL PQVMMILIPG QTLPLQLFHP QEVSMVRNLI QKDRTFAVLA YSNVQEREA QFGTTAEIYA YREEQDFGIE IVKVKAIGRQ RFKVLELRTQ SDGIQQAKVQ ILPECVLPST MSAVQLESLN K CQIFPSKP VSREDQCSYK WWQKYQKRKF HCANLTSWPR WLYSLYDAET LMDRIKKQLR EWDENLKDDS LPSNPIDFSY RV AACLPID DVLRIQLLKI GSAIQRLRCE LDIMNKCTSL CCKQCQETEI TTKNEIFSLS LCGPMAAYVN PHGYVHETLT VYK ACNLNL IGRPSTEHSW FPGYAWTVAQ CKICASHIGW KFTATKKDMS PQKFWGLTRS ALLPT

UniProtKB: Protein cereblon

-
Macromolecule #3: ELAV-like protein 1

MacromoleculeName: ELAV-like protein 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 9.383622 KDa
Recombinant expressionOrganism: Cloning vector pET-T7p(-3G)-lacO(SymR+1)-GFP-LVA (others)
SequenceString:
GDIGRTNLIV NYLPQNMTQD ELRSLFSSIG EVESAKLIRD KVAGHSLGYG FVNYVTAKDA ERAINTLNGL RLQSKTIKVS YARPS

UniProtKB: ELAV-like protein 1

-
Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Macromolecule #5: (3S)-3-[6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-1-benzofuran-...

MacromoleculeName: (3S)-3-[6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-1-benzofuran-3-yl]piperidine-2,6-dione
type: ligand / ID: 5 / Number of copies: 1 / Formula: A1EUN
Molecular weightTheoretical: 415.441 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: 4D-STEM / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

+
Image processing

CTF correctionType: NONE
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 484157
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

+
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