NEDD8 and ubiquitin ligation by cullin-RING E3 ligases

RING E3s comprise the largest family of ubiquitin (UB) and ubiquitin-like protein (UBL) ligases. RING E3s typically promote UB or UBL transfer from the active site of an associated E2 enzyme to a distally-recruited substrate. Many RING E3s - including the cullin-RING ligase family - are multifunctional, interacting with various E2s (or other E3s) to target distinct proteins, transfer different UBLs, or to initially modify substrates with UB or subsequently elongate UB chains. Here we consider recent structures of cullin-RING ligases, and their partner E2 enzymes, representing ligation reactions. The studies collectively reveal multimodal mechanisms - interactions between ancillary E2 or E3 domains, post-translational modifications, or auxiliary binding partners - directing cullinRING E3-E2 enzyme active sites to modify their specific targets.

Automated summary

In summary, RING E3s are the largest family of ubiquitin and ubiquitin-like protein ligases, typically working with E2 enzymes to transfer UB or UBL to specific substrates. Multifunctional RING E3s like cullin-RING ligase family have been shown to interact with various E2s to target distinct proteins or transfer different UBLs. The recent structures of cullin-RING ligases and their partner E2 enzymes reveal multimodal mechanisms directing these enzyme active sites to modify specific targets.