Post by CrystalsFirst

Our QualityPlus CRBNmidi is of crystallography-grade quality leading to crystals diffracting up to 1.9 Å and delivered structures with novel PROTAC warhead. ✅ Crystallizable ✅ SmartSoak® established ✅ Purity > 95% ✅ Monodisperse ✅ Melting temperature of 41°C Readily available CRBNmidi: https://lnkd.in/eqdiaTjU Structure and Function Cereblon (CRBN) functions as the substrate receptor of the Cullin 4–RING E3 ubiquitin ligase complex by coupling target recognition to ubiquitin transfer. Through its C-terminal thalidomide-binding domain, CRBN directly engages its substrates, bringing them and ubiquitin-loaded E2 into close proximity and positioning the target for polyubiquitination. Its native targets include many important endogenous substrates, such as adenosine monophosphate-activated protein kinase subunit α1, amyloid precursor protein or glutamine synthetase. Construct Design CRBNmidi (Kroupova et al., 2024) is a truncated CRBN construct that enables sufficient expression of soluble and stable protein in E. coli without additional factors. The truncated CRBNmidi still retains functionality similar to full-length wild-type CRBN and is therefore ideal for crystallographic and biophysical studies of CRBN-based PROTACs. CRBNmidi contains the Lon protease-like domain (Lon), spanning residues 41 - 187, followed by a Gly-Ser-Gly (GSG) linker that partially replaces the HB domain and connects the Thalidomide Binding Domain (TBD), which spans residues 249-426. The CRBNmidi construct also includes 12 stabilizing mutations (C78I, I92V, K116N, Q134E, R283W, C287N, V293S, G302D, L342R, C343E, T359I, L423I).