Figure 6.

The architecture and activation of CRL4. The CRL4 architecture (adapted from Fischer et al. [96]) is composed of the scaffold protein cullin 4, RBX1, DDB1, and a family of substrate-specific receptor proteins termed DCAFs (Ddb1- and Cul4-associated factors), which DDB2 and CSA are members. Upon binding to CPDs or 6-4PPs on the DNA strand via DDB2, or a protein target (e.g., CSB via CSA), CRL4 undergoes a conformation change that promotes CSN displacement and neddylation to activate the ligase.