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- EMDB-47270: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement -

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Basic information

Entry
Database: EMDB / ID: EMD-47270
TitleTernary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement
Map datadeepEMhancer
Sample
  • Complex: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement
KeywordsCRBN / molecular glue / E3 ligase / PDE6D / LIGASE
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsBaek K / Fischer ES
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA214608 United States
Damon Runyon Cancer Research FoundationDRG-2514-24 United States
CitationJournal: Nat Commun / Year: 2025
Title: Unveiling the hidden interactome of CRBN molecular glues.
Authors: Kheewoong Baek / Rebecca J Metivier / Shourya S Roy Burman / Jonathan W Bushman / Hojong Yoon / Ryan J Lumpkin / Julia K Ryan / Dinah M Abeja / Megha Lakshminarayan / Hong Yue / Samuel Ojeda ...Authors: Kheewoong Baek / Rebecca J Metivier / Shourya S Roy Burman / Jonathan W Bushman / Hojong Yoon / Ryan J Lumpkin / Julia K Ryan / Dinah M Abeja / Megha Lakshminarayan / Hong Yue / Samuel Ojeda / Yuan Xiong / Jianwei Che / Alyssa L Verano / Anna M Schmoker / Nathanael S Gray / Katherine A Donovan / Eric S Fischer /
Abstract: Induced proximity by molecular glues refers to strategies that leverage the recruitment of proteins to facilitate their modification, regulation or degradation. As prospective design of molecular ...Induced proximity by molecular glues refers to strategies that leverage the recruitment of proteins to facilitate their modification, regulation or degradation. As prospective design of molecular glues remains challenging, unbiased discovery methods are necessary to discover new chemical targets. Here we establish a high throughput affinity proteomics workflow leveraging E3 ligase activity-impaired CRBN-DDB1ΔB in cell lysates for the unbiased identification of molecular glue targets. By mapping the interaction landscape of CRBN-binding molecular glues, we unveil 298 protein targets and demonstrate the utility of enrichment methods for identifying targets overlooked by established methods. We use a computational workflow to estimate target confidence and perform biochemical and structural validation of uncharacterized neo-substrates. We further identify a lead compound for the previously untargeted non-zinc finger PPIL4 through a biochemical screen. Our study provides a comprehensive inventory of targets chemically recruited to CRBN and delivers a robust and scalable workflow for identifying drug-induced protein interactions in cell lysates.
History
DepositionOct 10, 2024-
Header (metadata) releaseAug 6, 2025-
Map releaseAug 6, 2025-
UpdateAug 6, 2025-
Current statusAug 6, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_47270.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationdeepEMhancer
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 288 pix.
= 316.8 Å
1.1 Å/pix.
x 288 pix.
= 316.8 Å
1.1 Å/pix.
x 288 pix.
= 316.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum-0.0017016877 - 2.0569868
Average (Standard dev.)0.00035938984 (±0.013435565)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 316.80002 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_47270_msk_1.map
Projections & Slices
AxesZYX

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Additional map: sharpened map

Fileemd_47270_additional_1.map
Annotationsharpened map
Projections & Slices
AxesZYX

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Additional map: 3d refinement

Fileemd_47270_additional_2.map
Annotation3d refinement
Projections & Slices
AxesZYX

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Half map: halfmap1

Fileemd_47270_half_map_1.map
Annotationhalfmap1
Projections & Slices
AxesZYX

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Slices (1/2)
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Half map: halfmap2

Fileemd_47270_half_map_2.map
Annotationhalfmap2
Projections & Slices
AxesZYX

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Sample components

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Entire : Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement

EntireName: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement
Components
  • Complex: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement

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Supramolecule #1: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement

SupramoleculeName: Ternary complex of CRBN-DDB1-PDE6D with FPFT-2216 local refinement
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 51.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 515636
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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