Abstract:

The ubiquitin system plays important roles in many physiological processes in eukaryotes. In this talk, I will present our recent progress on structural and functional characterizations of two important molecular machines involved in the ubiquitin system, p97 and Ubr1. p97 is a type-II AAA ATPase and acts as a central hub to process various ubiquitinated substrates in the ubiquitin system. Human p97 is associated with several neurodegenerative diseases and is also a cancer drug target. Ubr1 is the first genetically cloned E3 ligase, and is involved in the N-degron pathway. We used single-particle cryo-EM as a major tool to determine their structures in complex with the ubiquitinated substrates in multiple states, which provided mechanistic insights into these molecular machines.