Fig 1. SCF-mediated substrate degradation and Cand1 cycle.

A: Scheme of SCF-mediated substrate degradation: (1) Substrate (S) binding to substrate receptors (Skp1/SR) and UBC12-mediated neddylation (N8) of Cul1, (2) E2 recruitment, ubiquitin (Ub) transfer by E2 to the substrate and Ub chain elongation, (3) substrate degradation by the 26S proteasome and (4) deneddylation of Cul1 by the COP9 signalosome. Relative sizes of protein subunits are not to scale. B: Model of the Cand1-mediated exchange cycle for two substrate receptors (Skp1/SR1 and Skp1/SR2). K_sr, K_ca, $K_{sr}^{\prime }$ and $K_{ca}^{\prime }$ denote dissociation constants whereas k_sr, k_ca, $k_{sr}^{\prime }$ and $k_{ca}^{\prime }$ are dissociation rate constants (cf. Table 1). The parameter η, defined in Eq (2), measures the preference of Cand1 and SR for binding to Cul1. Similarly, α and β account for relative differences in the dissociation rate constants for the binary complexes (α) and the ternary complex (β).