Structure of Parkin Rcat domain bound to ubiquitin

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD is caused by genetic predispositions leading to neuronal cell death. Dysfunction of damaged mitochondrial turnover by mitophagy (mitochondrial autophagy) and the ubiquitin-proteasome system has been found in most cases of genetic PD. The ubiquitin-proteasome system mediates protein degradation trough ubiquitination – a post-translational modification involving a series of ubiquitin (Ub) transfer steps among a variety of enzymes. Interaction between Ub and an E3 ligase occurs before a final covalent transfer of Ub to substrate. Parkin is a mitochondrial E3 ligase that plays a vital role in regulating mitophagy and the ubiquitin-proteasome system. Currently, no information exists about the structure of ubiquitin-conjugated parkin. The main goal of this project is to determine the atomic level structure of Parkin bound to ubiquitin. This structure could be used to design small molecule modulators of parkin-mediated ubiquitination. A bigger view of this project has been actively involved providing a better quality of life for patients and their families.

Faculty Supervisor:

Gary Shaw

Student:

Partner:

University of Glasgow

Discipline:

Life Sciences

Sector:

Education

University:

Western University

Program: