null Jean-François Trempe, PhD
Proteomics • structural biology • Parkinson's disease • crystallography • NMR • mass spectrometry
My research focuses on the structure and pharmacology of proteins implicated in Parkinson’s disease, in particular Parkin and PINK1. Mutations in those proteins cause early-onset familial forms of the disease. Parkin and PINK1 function together in a quality control pathway that segregates and degrades damaged mitochondria, which are required for neuronal survival. Through biochemical studies we have discovered how Parkin is activated by PINK1, and we are using its 3D structure to design strategies to rescue pathogenic mutations in Parkin. My group is also exploring how PINK1 can detect damaged mitochondria and how its structure can be used to design therapeutic molecules. Finally, we are using proteomics and mass spectrometry to understand the molecular mechanisms of proteins that regulate PINK1, such as the mitochondrial processing peptidase, and determine the role of Parkin/PINK1 in mitochondrial damage clearance in stem cell-derived neurons and animal models of Parkinson.
Bayne AN, Trempe J-F (2019) Mechanisms of PINK1, ubiquitin and Parkin interactions in mitochondrial quality control and beyond. Cellular and Molecular Life Sciences, 76: 4589-4611. PMID: 31254044.
Rasool S, Trempe J-F (2018). New insights into the structure of PINK1 and the mechanism of ubiquitin phosphorylation. Critical Reviews in Biochemistry and Molecular Biology. 21: 1-20. PMID: 30238821.
Rasool S, Soya N, Truong L, Croteau N, Lukacs G, Trempe J-F (2018). PINK1 autophosphorylation is required for ubiquitin recognition. EMBO Reports, 19: e44981. PMID: 29475881.
Tang MY, Vranas M, Krahn AI, Pundlik S, Trempe J-F, Fon EA (2017) Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation. Nature Communications, 8:14697. PMID: 28276439.
Trempe J-F, Sauvé V, Grenier K, Seirafi M, Tang MY, Ménade M, Al-Abdul-Wahid S, Krett J, Wong K, Kozlov G, Nagar B, Fon EA, Gehring K (2013) Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science, 340: 1451-1455. PMID: 23661642.