Active, Recombinant, Neddylated Human CUL3 / RBX1 Complex

Background: Cullin-3 (CUL3) is a central scaffold protein in CUL3–BTB E3 ubiquitin ligase complexes that control the ubiquitylation and turnover of proteins involved in cytoskeletal organization, membrane trafficking, redox homeostasis, and signal transduction. Within these complexes, CUL3 structurally bridges BTB-domain substrate-recognition adaptors (often BTB–Kelch or other BTB proteins) with the RBX1 RING subunit, thereby positioning both the bound substrate and an E2 ubiquitin‑conjugating enzyme to promote efficient ubiquitin transfer. Biologically, CUL3 is crucial for processes such as neuronal development, ion channel regulation, stress responses, and proper cell morphology, and its dysregulation has been implicated in neurological disorders, cancer, and cardiovascular disease. In vivo, CUL3 E3 ligase activity depends on covalent attachment of NEDD8 (neddylation) to the CUL3 subunit, which activates the complex and modulates its interactions and conformational dynamics.