In vitro reconstitution of Parkin-mediated mitochondria quality control
| Project/Area Number |
26650042
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
MATSUDA Noriyuki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (10332272)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | PINK1 / Parkin / ユビキチン / ミトコンドリア / パーキンソン病 / 再構成 |
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| Outline of Final Research Achievements |
Parkin, a gene product mutated in familial Parkinsonism, is essential for elimination of damaged mitochondria. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin by PINK1 are crucial for their function. However, the mechanism by which phosphorylated ubiquitin associates with and activates Parkin remains largely unknown.
Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that IBR domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, the Fluoppi assay showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells.
Thus molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry reveals that a novel binding mechanism between Parkin and ubiquitin.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Ubiquitin is phosphorylated by PINK1 to activate parkin.2014
Author(s)
Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., Endo, T., Fon. E. A., Trempe, J. F., Saeki, Y., Tanaka, K., and Matsuda, N.
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Journal Title
Nature
Volume: 510(in press)
Issue: 7503
Pages: 162-166
DOI
Related Report
Peer Reviewed
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