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

• DOI: 10.1038/s41467-024-52871-9
• Publication Date: 2024-10-15T14:43:21Z
• Authors: Alena Kroupova; Valentina A. Spiteri; Zoe J. Rutter; Hirotake Furihata; Darren Darren; Sarath Ramachandran; Sohini Chakraborti; Kevin Haubrich; Julie Pethe; Denzel Gonzales; Andre J. Wijaya; Maria Rodriguez-Rios; Manon Sturbaut; Dylan M. Lynch; William Farnaby; Mark A. Nakasone; David Zollman; Alessio Ciulli
• Keywords: Cereblon

The ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide recruited by most targeted protein degraders (PROTACs molecular glues) in clinical development. Biophysical structural investigation CRBN has been limited current constructs that either require co-expression with adaptor DDB1 or inadequately represent full-length protein, high-resolution structures degrader ternary complexes remaining rare. We present design