Ubiquitin-ligating enzyme

While there is usually only one El enzyme, many species of E2 proteins and multiple families of E3 enzymes or E3 multiprotein complexes exist. Selection of substrates for ubiquitin-ligation occurs mainly by specific E3 enzymes which target substrate proteins that contain specific recognition signals (fig. 2.15B). E3 enzymes also can bind indirectly to the substrate, via an adaptor protein. 

The hgases involved in this type of ubiquitin ligation are organized in multiprotein complexes caUed SCF complexes (Skpl, cuUin, F box protein). In S. cerevisiae, the complex is composed of the proteins Cdc24 (an E2 enzyme), Cdc53 and Skpl, which form the core of the SCF. This core associates in a variable maimer with a further type of protein, which function as specific substrate recognition factors. A common feature of these proteins is a sequence element known as the F box (review Peters, 1998). Consequently, multiple forms of SCF complexes exist, due to this variable association. 

Histones are also modified by the small ubiquitin-like modifier (SUMO). SUMO-speeifie aetivating, eonjugating and ligating enzymes catalyse the ligation of SUMO proteins to lysines in histones, particularly in histone H4, where SUMOylation is associated with transcriptional repression, through the recruitment of HDACs and HPl. ... 

Two of the four different E3 enzymes mentioned in the text are shown. The cyclosome/anaphase promoting complex (APC) ligates ubiquitin to regulatory and structural cell cycle proteins containing a destruction box as recognition signal (see also 13.3.2). The activity of the APC is thought to be controlled by phosphorylation. Eor simplicity, the subunits of APC are not shown. 

Selection of a protein for Ub-dependent proteolysis occurs particularly via the E3 enzymes of the ubiquitin pathway (see 2.7.2) that catalyzes ligation of the target protein with ubiquitin. The specificity of Ub-protein ligation is determined by the nature of the E3 enzymes, which may be composed of several subunits. The composition of this complex is very variable and can be changed according to requirements. 

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