Figure 4.

Cullin-RING ligases (CRLs). Simplified diagram of CRL structure. The cullin forms the backbone of the CRL complex. Cullin homology domains at the carboxyl-terminus are required for binding to the E3 and the amino-terminus interacts with the substrate adaptor proteins where required (there is no known substrate adaptor for CUL3) [242]. Neddylation of the cullins on a conserved carboxyl-terminal lysine induces conformational changes to promote ubiquitylation of CRL substrates. SKP1 and DDB1 are the substrate adaptor proteins for CRL1 and CRL4 complexes, respectively. F-box proteins and DCAFs are the substrate receptors for CRL1 and CRL4 complexes, respectively. See text for more details.