Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders

Kroupova A, Spiteri V, Rutter Z, Furihata H, Darren D, Ramachandran S, Chakraborti S, Haubrich K, Pethe J, Gonzales D, Wijaya A, Rodriguez-Rios M, Sturbaut M, Lynch D, Farnaby W, Nakasone M, Zollman D, Ciulli A
Nature Communications 15(1) (2024 Oct 15)

doi: 10.1038/s41467-024-52871-9
Submitted to SASBDB: 2024 Jan 17
Published in SASBDB:

SASDU52 – Cereblon-midi (CRBNmidi), an engineered Cereblon construct for crystallographic and biophysical studies, apo form

Cereblon-midi experimental SAS data
SWISSMODEL model
Sample: Cereblon-midi monomer, 37 kDa protein
Buffer: 20 mM Hepes, 500 mM NaCl, 0.5 mM TCEP, pH: 7.5
Experiment: SAXS data collected at B21, Diamond Light Source on 2023 Mar 1
RgGuinier 2.7 nm
Dmax 8.6 nm
VolumePorod 61 nm3

SASDU62 – Cereblon-midi (CRBNmidi), an engineered Cereblon construct for crystallographic and biophysical studies, bound to Mezigdomide

Cereblon-midimezigdomide experimental SAS data
PYMOL model
Sample: Cereblon-midi monomer, 37 kDa protein
Mezigdomide monomer, 1 kDa synthetic construct
Buffer: 20 mM Hepes, 500 mM NaCl, 0.5 mM TCEP, pH: 7.5
Experiment: SAXS data collected at B21, Diamond Light Source on 2023 Mar 1
RgGuinier 2.3 nm
Dmax 7.3 nm
VolumePorod 60 nm3

SASDU72 – Cereblon-midi (CRBNmidi), an engineered Cereblon construct for crystallographic and biophysical studies, bound to Pomalidomide

Cereblon-midipomalidomide experimental SAS data
Cereblon-midi pomalidomide Kratky plot
Sample: Cereblon-midi monomer, 37 kDa protein
Pomalidomide monomer, 0 kDa synthetic construct
Buffer: 20 mM Hepes, 500 mM NaCl, 0.5 mM TCEP, pH: 7.5
Experiment: SAXS data collected at B21, Diamond Light Source on 2023 Mar 1
RgGuinier 2.3 nm
Dmax 6.9 nm
VolumePorod 63 nm3

SASDU82 – Cereblon-midi (CRBNmidi), an engineered Cereblon construct for crystallographic and biophysical studies, bound to Iberdomide

Cereblon-midiIberdomide experimental SAS data
Cereblon-midi Iberdomide Kratky plot
Sample: Cereblon-midi monomer, 37 kDa protein
Iberdomide monomer, 0 kDa synthetic construct
Buffer: 20 mM Hepes, 500 mM NaCl, 0.5 mM TCEP, pH: 7.5
Experiment: SAXS data collected at B21, Diamond Light Source on 2023 Mar 1
RgGuinier 2.4 nm
Dmax 7.7 nm
VolumePorod 68 nm3

SASDU92 – Cereblon-midi (CRBNmidi), an engineered Cereblon construct for crystallographic and biophysical studies, bound to Lenalidomide

Cereblon-midiLenalidomide experimental SAS data
Cereblon-midi Lenalidomide Kratky plot
Sample: Cereblon-midi monomer, 37 kDa protein
Lenalidomide monomer, 0 kDa synthetic construct
Buffer: 20 mM Hepes, 500 mM NaCl, 0.5 mM TCEP, pH: 7.5
Experiment: SAXS data collected at B21, Diamond Light Source on 2023 Mar 1
RgGuinier 2.2 nm
Dmax 6.2 nm
VolumePorod 59 nm3