Poly-ubiquitination reactions by monomeric and dimeric SCF complexes. Diagram of poly-ubiquitin conjugation to a substrate (rectangle) by monomeric (A) and dimeric (B) SCF complexes. Top panels, E2 with activated ubiquitin prior to binding. Middle panels, E2 with activated ubiquitin loaded onto E3 but prior to transfer of ubiquitin to substrate. Bottom panels, the substrate has a three-ubiquitin chain and a new E2 with activated ubiquitin has docked. Note how the ability of E2s to load onto both sites of the dimeric SCF complex facilitates the addition of ubiquitin onto the growing polyubiquitin chain. In the diagram, the addition of the first ubiquitin is more sterically favorable from the E2 docking site that is closer to the substrate, while additions to the elongated polyubiquitin chain are more favorable from the more distant E2 docking site. Proteins are labeled as in Fig. 1.