Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity

Localization, activity and lifespan of a protein are signaled by a small, 8 kDa protein, ubiquitin (Ub). Ub conjugation is a post-translational modification orchestrated by the sequential action of activating (E1), conjugating (E2), and ligating (E3) enzymes. Although a simple combination of an E2 and an E3 enzyme can be sufficient for an active complex, in other cases ubiquitination can occur in the context of large multimeric complexes with enhanced molecular abilities. Here, we review several Ub ligase complexes to highlight strategies governing conjugational specificity, the gained adaptability in substrate specificity, and modulatory flexibility encoded in regulatory components of these diverse multimers.