Elucidation of thermal fluctuation associated with structural transition from amorphous aggregation to amyloid fibrillation
| Project/Area Number |
17K07363
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Osaka University |
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Principal Investigator |
SASAHARA KENJI 大阪大学, 蛋白質研究所, 特任講師(常勤) (20432495)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アミロイド線維 / アミロイドーシス / 蛋白質凝集 / アミロイド / 蛋白質 / 揺らぎ / アモルファス凝集 |
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| Outline of Final Research Achievements |
Using three types of proteins (hen lysozyme, β2-microglobulin, α-synuclein), the relation between structural fluctuation and amyloid fibril formation was examined. In the experimental system, the structural fluctuation of the proteins was regulated by the heating and the addition of polyphosphate. Upon binding of polyphosphate to the protein molecules, the protein solubility largely decreased, resulted in the structurally-fluctuated state of the protein molecules in the vicinity of solubility limit. It was found that amyloid fibril formation is efficiently induced from the fluctuated state through the perturbation such as agitation. The model of amyloid fibril formation based on the structural fluctuation of protein was presented.
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| Academic Significance and Societal Importance of the Research Achievements |
蛋白質は、大きく二つの凝集体を形成する。規則構造を持たないアモルファス凝集と規則的なクロスβシート構造を持つアミロイド線維である。生体内でのアミロイド線維の沈着は、アルツハイマー病、パーキンソン病、Ⅱ型糖尿病、プリオン病など数々の深刻な病気に関わることで注目されている。本研究では、蛋白質の構造揺らぎに着目して、天然状態にある蛋白質がアミロイド線維を形成する機構、及びアモルファス凝集を回避してアミロイド線維が形成される機構を明らかにした。蛋白質の構造揺らぎの概念を導入した新たなアミロイド形成モデルを示した。結果は、アミロイド病の治療や予防に結び付き、また早期診断にも応用可能である
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Report
(4 results)
Research Products
(16 results)
