2012
DOI: 10.1002/humu.22127
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Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1 (PINK1)

Abstract: 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… Show more

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Cited by 32 publications
(32 citation statements)
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References 108 publications
(181 reference statements)
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“…4B). The kinase domain of the obtained PINK1 structure was in good agreement with previous models (Beilina et al , 2005; Mills et al , 2008; Cardona et al , 2011; Sim et al , 2012; Trempe and Fon, 2013). In addition, our model also contained the N-terminal region that regulates import, sub-mitochondrial localization, and turnover of PINK1.…”
Section: Resultssupporting
confidence: 88%
See 1 more Smart Citation
“…4B). The kinase domain of the obtained PINK1 structure was in good agreement with previous models (Beilina et al , 2005; Mills et al , 2008; Cardona et al , 2011; Sim et al , 2012; Trempe and Fon, 2013). In addition, our model also contained the N-terminal region that regulates import, sub-mitochondrial localization, and turnover of PINK1.…”
Section: Resultssupporting
confidence: 88%
“…To model PINK1 protein, its dynamics and enzymatic activity, we used a combination of methods that have been applied before to predict mutational effects and activation conformations of human parkin (Caulfield et al , 2014, 2015; Fiesel et al , 2015 b ), which were in good agreement with the latest structures of an activated form of the E3 ubiquitin ligase (Kumar et al , 2015; Sauve et al , 2015; Wauer et al , 2015). The C-terminus of our PINK1 model is very similar to structures of homologous kinases and existing models of the PINK1 kinase domain (Beilina et al , 2005; Mills et al , 2008; Cardona et al , 2011; Sim et al , 2012; Trempe and Fon, 2013). …”
Section: Discussionmentioning
confidence: 52%
“…Two evolutionarily conserved autophosphorylation sites within the kinase domain have been shown to promote parkin recruitment to depolarized mitochondria. also support the prediction that conserved regions of PINK1 at residues 8-18 and 67-77 contain potential MPP cleavage motifs (97), although the involvement of MPP has been controversial (6,55). AFG3L2 (m-AAA catalytic subunit) has been suggested as the protease producing the DN 2 fragment (*45 kDa band) (39,100).…”
Section: Structure and Processing Of Pink1supporting
confidence: 65%
“…This chaperone system promotes folding of many kinases and has been shown to regulate stability and subcellular distribution of PINK1 [69, 70, 77, 78]. Mutations such as p.L347P that showed reduced binding to HSP90/CDC37 [71, 79] were suggested before to be subject to misfolding and increased turnover through either the Ub/proteasome system or another protease [66].…”
Section: Discussionmentioning
confidence: 99%