8tnp

Cryo-EM structure of DDB1dB:CRBN:Pomalidomide:SD40

Method: ELECTRON MICROSCOPY Dmax: 114.5 Å Quality: GOOD

1. Protein Identity and Related Structures Protein Identity & Related Structures

Protein cereblon

Homo sapiens

UniProt Q96SW2

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Insufficient information Heteromer Protein × 3 PDB declaration: trimeric(3) Consistent with protein copy count Chain B; UniProt 1–442 Not recorded DNA damage-binding protein 1 × 1 (Q16531) Maltose/maltodextrin-binding periplasmic protein,SD40 × 1 (P0AEX9,Q13422) ZN ZINC ION × 2 Y70 S-Pomalidomide × 1 ELECTRON MICROSCOPY cryo-EM buffer:pH 7;20 mM HEPES/NaOH pH 7.0, 150 mM NaCl, and 3 mM TCEP. DMSO concentrations were kept below 2% (v/v) cryo-EM vitrification conditions:Cryogen ETHANE;Leica EM-GP plunge freezer with chamber conditions of 10 C and 90% relative humidity. Grids were first pre-incubated with 4 uL of 10 uM CRBN-agnostic IKZF1_140-196_Q146A,G151N for 1 minute and then blotted from behind for 4 s. Immediately, 4 uL of mixture 1 diluted 10-fold--with the dilution buffer during the 1-minute incubation time--was applied to the grids before blotting for 4 s and plunging into liquid ethane at -181 C. Resolution 3.30 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

93 other PDB entries and 141 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name CRBN_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain B; PDBConstruct 44–485; UniProt 1–442

DNA damage-binding protein 1

Homo sapiens

UniProt Q16531

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Insufficient information Heteromer Protein × 3 PDB declaration: trimeric(3) Consistent with protein copy count Chain A; UniProt 1–395 Chain A; UniProt 706–1140 Mutation:residues 396-705 deleted Protein cereblon × 1 (Q96SW2) Maltose/maltodextrin-binding periplasmic protein,SD40 × 1 (P0AEX9,Q13422) ZN ZINC ION × 2 Y70 S-Pomalidomide × 1 ELECTRON MICROSCOPY cryo-EM buffer:pH 7;20 mM HEPES/NaOH pH 7.0, 150 mM NaCl, and 3 mM TCEP. DMSO concentrations were kept below 2% (v/v) cryo-EM vitrification conditions:Cryogen ETHANE;Leica EM-GP plunge freezer with chamber conditions of 10 C and 90% relative humidity. Grids were first pre-incubated with 4 uL of 10 uM CRBN-agnostic IKZF1_140-196_Q146A,G151N for 1 minute and then blotted from behind for 4 s. Immediately, 4 uL of mixture 1 diluted 10-fold--with the dilution buffer during the 1-minute incubation time--was applied to the grids before blotting for 4 s and plunging into liquid ethane at -181 C. Resolution 3.30 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

202 other PDB entries and 290 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name DDB1_HUMAN
Isoform
PDB entities 2
Chains and sequence ranges Author chain A; PDBConstruct 25–419; UniProt 1–395 Author chain A; PDBConstruct 426–860; UniProt 706–1140

Maltose/maltodextrin-binding periplasmic protein,SD40

Homo sapiens

UniProt P0AEX9

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Insufficient information Heteromer Protein × 3 PDB declaration: trimeric(3) Consistent with protein copy count Chain C; UniProt 27–396 Mutation:engineered to enhance binding of cereblon/DDB1 in the presence of IMiD derivatives Protein cereblon × 1 (Q96SW2) DNA damage-binding protein 1 × 1 (Q16531) ZN ZINC ION × 2 Y70 S-Pomalidomide × 1 ELECTRON MICROSCOPY cryo-EM buffer:pH 7;20 mM HEPES/NaOH pH 7.0, 150 mM NaCl, and 3 mM TCEP. DMSO concentrations were kept below 2% (v/v) cryo-EM vitrification conditions:Cryogen ETHANE;Leica EM-GP plunge freezer with chamber conditions of 10 C and 90% relative humidity. Grids were first pre-incubated with 4 uL of 10 uM CRBN-agnostic IKZF1_140-196_Q146A,G151N for 1 minute and then blotted from behind for 4 s. Immediately, 4 uL of mixture 1 diluted 10-fold--with the dilution buffer during the 1-minute incubation time--was applied to the grids before blotting for 4 s and plunging into liquid ethane at -181 C. Resolution 3.30 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

366 other PDB entries and 491 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name MALE_ECOLI
Isoform
PDB entities 3
Chains and sequence ranges Author chain C; PDBConstruct 29–398; UniProt 27–396

Maltose/maltodextrin-binding periplasmic protein,SD40

Homo sapiens

UniProt Q13422

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Insufficient information Heteromer Protein × 3 PDB declaration: trimeric(3) Consistent with protein copy count Chain C; UniProt 143–178 Mutation:engineered to enhance binding of cereblon/DDB1 in the presence of IMiD derivatives Protein cereblon × 1 (Q96SW2) DNA damage-binding protein 1 × 1 (Q16531) ZN ZINC ION × 2 Y70 S-Pomalidomide × 1 ELECTRON MICROSCOPY cryo-EM buffer:pH 7;20 mM HEPES/NaOH pH 7.0, 150 mM NaCl, and 3 mM TCEP. DMSO concentrations were kept below 2% (v/v) cryo-EM vitrification conditions:Cryogen ETHANE;Leica EM-GP plunge freezer with chamber conditions of 10 C and 90% relative humidity. Grids were first pre-incubated with 4 uL of 10 uM CRBN-agnostic IKZF1_140-196_Q146A,G151N for 1 minute and then blotted from behind for 4 s. Immediately, 4 uL of mixture 1 diluted 10-fold--with the dilution buffer during the 1-minute incubation time--was applied to the grids before blotting for 4 s and plunging into liquid ethane at -181 C. Resolution 3.30 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

9 other PDB entries and 12 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name IKZF1_HUMAN
Isoform
PDB entities 3
Chains and sequence ranges Author chain C; PDBConstruct 420–455; UniProt 143–178

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

SAXS scattering curve SAXS Profile

SAXS profile for 8tnp

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 8tnp
Download Download

2. Structure Basics 2. Structure Basics

Entry ID entry_id8tnp
Deposition date deposition_date2023-08-02
Structure title titleCryo-EM structure of DDB1dB:CRBN:Pomalidomide:SD40
Keywords keywordsubiquitin, CRBN, directed evolution, Zinc finger, IMiD, Molecular Glue, TRANSFERASE; TRANSFERASE
Experimental Method methodELECTRON MICROSCOPY

3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier34.99
Radius of gyration Rg (electron density) rg_electron34.25
Forward intensity I(0) i0261244000.00
Molecular weight molecular_weight131590.0 kDa
Excluded volume excluded_volume165420 ų
Envelope volume envelope_volume212390 ų
Hydration-shell volume shell_volume51134 ų
Envelope diameter envelope_diameter122.9
Shell Rg shell_rg41.17
Envelope Rg envelope_rg34.23
Shape Rg shape_rg34.23
Total Rg total_rg34.80
Total atoms total_atoms18477
Residues n_residues1159
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 −1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3

4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax114.5
Rg (real space) rg_real34.92
Rg uncertainty (real space) rg_real_error0.92
I(0) (real space) i0_real2.6120e+08
I(0) uncertainty (real space) i0_real_error4.6440e+06
Rg (reciprocal space) rg_reciprocal34.96
I(0) (reciprocal space) i0_reciprocal261300000.0000
Solution quality estimate total_estimate0.8948
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary40.7
Skewness Skewness skewness0.277
Kurtosis Kurtosis kurtosis-0.456
Angular range angular_range— – 0.2250 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha62600000.0000
Real-space data points n_real_points46
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.889; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 1.000; Smooth: 0.959

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (5)

8. Citations (1)

9. Files and Curves (10)