| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Outline of Final Research Achievements |
Ubiquitin is a protein with high structural stability and solubility. However, upon thermal and hydrodynamic stress, its polymerized form, a polyubiquitin chain, forms fibrillar aggregates that are associated with neurodegenerative diseases such as Alzheimer’s disease. In this study, we investigated the structure and formation mechanism of polyubiquitin fibrils at atomic resolution by using nuclear magnetic resonance. In our analysis of fibril intermediates and hydrogen-deuterium exchange experiments of fibrils, we identified important structural changes and inter-molecular interactions in the formation of polyubiquitin fibrils. Furthermore, we established a new rheological nuclear magnetic resonance to monitor fibril formation in situ and detected conformational changes of side chains in polyubiquitin chains during their fibril formation.
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