Model of the SCF in Complex With E2 and Substrates

SCF -CyclinE-E2 complexes [66, 85, 103]. In all cases, no intermolecular collision was found in the final models. The substrate-binding domains of all three F-box proteins are positioned on the same side of the SCF complex as the E2. In addition, these domains are all oriented toward the E2 active site. Remarkably, the positions of the WD40 domain in the and SCF models are strikingly 

Even with the uncertainty in E2 active-site position, the models have suggested that there would be no E3 residues near the E2 active site, in agreement with the observations made in the c-Cbl-E2 structure. This again ruled out the possibility that the SCF E3 provides acid/base catalysis and the possibility that the SCF positions the -amino group of the lysine at the E2 active site [66]. The only plausible mechanism left accounting for the catalysis mediated by the SCF in substrate ubiq-uitination is that the E3 complex helps increase the effective concentration of a portion of the substrate that contains the physiological ubiquitination-site lysine at the E2 active site. This model made the testable prediction that the distance between the destruction motif and the ubiquitinated lysine is a determinant of the ubiquiti-nation efficiency. 

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