Active, Recombinant Human KLHDC2 / EloB / EloC Complex

Background: Kelch Domain Containing 2 (KLHDC2) is a substrate receptor for the CUL2-RBX1 Cullin-RING E3 ubiquitin ligase complex, where it forms a stable heterotrimer with the adaptor proteins Elongin B (EloB) and Elongin C (EloC). KLHDC2 recognizes proteins bearing specific C-terminal degron motifs, particularly diglycine-ending (GG) peptides, and recruits them for ubiquitylation and subsequent proteasomal degradation through the C-degron pathway. This highly selective substrate recognition mechanism has made KLHDC2 an attractive E3 ligase for targeted protein degradation (TPD), including the development of molecular glues and PROTACs that exploit its unique degron-binding pocket. The recombinant KLHDC2 / EloB / EloC complex provides a biologically relevant substrate receptor module for biochemical, biophysical, and structural studies of CUL2-dependent ubiquitylation, degron recognition, ligand discovery, and targeted protein degradation.