Proposed models for dimerization of CRL complexes. (A) Diagram of an SRS-mediated dimeric SCF complex. Dimerization is mediated by interactions between the SRSs in each CRL. This structure has been experimentally confirmed . (B) Diagram of a Nedd8-cullin-based dimeric CRL3 complex. Dimerization is mediated by interaction between Nedd8, which is covalently linked to one CUL3 protein, and the WH-B domain of an unneddylated CUL3 . The overall structure of the Nedd8-cullin-based dimer has not been determined. The dimer is drawn in a head-to-head conformation to accommodate the binding of a dimeric SRS to the two CUL3 N-termini (as many CRL3 SRSs are constitutively dimeric in vivo). (C) Diagram of a monomeric CRL2 complex binding a dimeric SRS. The existence of such a structure has not yet been directly confirmed by experiments (see text). Proteins are labeled as in Fig. 1.