Fig. 8: Mode of action of PRT1 E3 Ub ligase.
a Conformational change of two PRT1ZZ loops, L2 and L3, upon complex formation with the N-degron substrate, while L1 maintains position as a rigid frame. b Active RING1-RING2 heterodimer interacts with the UBC8 E2 Ub-conjugating enzyme and Ub, which forms a competent ternary complex for ubiquitylation. The ZZ domain at the C-terminal region of PRT1 grabs the Tyr61-BB substrate through its bulky hydrophobic N-degron (Nt tyrosine). The flexibility between ZZ and RING domains enables the efficient delivery of the substrate to RING1, which interacts with the E2 enzyme and Ub. The red star represents the ubiquitylation reaction, and several rounds of reaction generate the poly-ubiquitylated Tyr61-BB.
