Protein ubiquitylation is a pervasive post-translational modification that plays a crucial role in most signalling pathways. This is because the addition of ubiquitin can alter protein stability and function, allowing cells to respond to changes in their environment. The action of ubiquitin E2 conjugating enzymes and ubiquitin E3 ligases is essential for the modification of proteins with ubiquitin and is central to most cellular processes.
E3 ligases are the final enzymes in the cascade and have a key role in ubiquitin transfer as they select both the substrate for modification and the E2 that will specify the type of chain added. Most E3 ligases have a RING domain that interacts with the E2 and is required for the addition of ubiquitin, although other domains in the E3 also have important roles in regulating activity.
Many RING E3 ligases have zinc finger domains adjacent to the RING domain and recent work in my laboratory has focused on revealing the role of these domains. Here I will present our data that highlights roles for zinc finger domains in both E2 recruitment and activation of the E2~Ub conjugate.