Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1 (PINK1)
AuthorSim, Chou Hung; Gabriel, Kipros; Mills, Ryan D.; Culvenor, Janetta G.; Cheng, Heung-Chin
Source TitleHuman Mutation
AffiliationBiochemistry and Molecular Biology
Department of Biochemistry and Molecular Biology
Bio21 Molecular Science and Biotechnology Institute
3Department of Pathology
Document TypeJournal Article
CitationsSim, C. H., Gabriel, K., Mills, R. D., Culvenor, J. G., & Cheng, H. (2012). Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1 (PINK1). Human Mutation, 33(10), 1408-1422.
Access StatusThis item is currently not available from this repository
NHMRC Grant codeNHMRC/566751
The research outputs in this collection have been funded in whole or in part by the National Health and Medical Research Council (NHMRC).
Mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene can cause early-onset familial Parkinson disease (PD). PINK1 encodes a neuroprotective protein kinase localized at the mitochondria, and its involvement in regulating mitochondrial dynamics, trafficking, structure, and function is well documented. Owing to the lack of information on structure and biochemical properties for PINK1, exactly how PINK1 exerts its neuroprotective function and how the PD-causative mutations impact on PINK1 structure and function remain unclear. As an approach to address these questions, we conducted bioinformatic analyses of the mitochondrial targeting, the transmembrane, and kinase domains of PINK1 to predict the motifs governing its regulation and function. Our report sheds light on how PINK1 is targeted to the mitochondria and how PINK1 is cleaved by mitochondrial peptidases. Moreover, it includes a potential optimal phosphorylation sequence preferred by the PINK1 kinase domain. On the basis of the results of our analyses, we predict how the PD-causative mutations affect processing of PINK1 in the mitochondria, PINK1 kinase activity, and substrate specificity. In summary, our results provide a conceptual framework for future investigation of the structural and biochemical basis of regulation and the neuroprotective mechanism of PINK1.
KeywordsParkinson's disease; neuronal death; PINK1; protein kinase
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References