Title
Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation
Author
Jacob D. Aguirrea, Karen M. Dunkerleya, Pascal Merciera, Gary S. Shaw
Year
2016
Journal
PNAS
Abstract
Parkinson’s disease is a devastating neurodegenerative disorder that can be inherited through mutations in genes encoding the kinase PTEN-induced kinase 1 (PINK1) or the ubiquitin ligase parkin. Parkin exhibits neuroprotective properties by ubiquitinating proteins on damaged mitochondria, leading to their turnover. However, parkin exists in an inactive state that must be alleviated by PINK1 phosphorylation. Therefore, the molecular interpretation of the phosphorylation signal is immensely valuable to our understanding of parkin’s role in mitochondrial maintenance and neuronal fidelity. We present the 3D structure of the phosphorylated inhibitory domain of parkin and describe the structural changes that lead to activation of the enzyme. Alongside the available phosphoubiquitin structure, this study completes a structural picture of PINK1-orchestrated parkin activation in impaired mitochondria.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Thermal stability, Chemical stability, Protein denaturation, Biochemistry