2019 Fiscal Year Final Research Report
Residual structure in intrinsically disordered protein and its function
| Project/Area Number |
16K08204
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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 |
Physical pharmacy
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| Research Institution | Teikyo Heisei University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 天然変性蛋白質 / NMR / 残存構造 / アミドプロトン交換 / シグナル強度 / 温度変化 |
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| Outline of Final Research Achievements |
Alpha-synuclein in solution is not folded even under the physiological condition. It becomes the fibril, which causes the Parkinson’s disease. The A30P or A53T mutation is frequently found in the genetically familial patients with the change of the kinetics of the fibril formation.
Amide-proton exchange and signal intensity were employed for the detection of the residual structures. Temperature effects were also obtained for the data. The more flexible structure was observed at the C-terminal region of A30P than WT. By contrast, more rigid structures were observed in mutants at 30-60 region, indicating that the core for the fibril formation was formed. The residual structure even for the intrinsically disordered protein was observed by NMR. The interaction between the N-terminal and C-terminal regions might occur in solution.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
αシヌクレインは天然変性蛋白質に分類され、その研究は医学生化学分野において重要な意義を持つ。30％の蛋白質はこの種の天然変性蛋白質に属し生命現象に関わる。通常は変性状態で、他の蛋白質との結合とともに構造形成するというユニークな特性を持つことより、物理化学的にも研究は意義を持つ。本研究により、構造形成前と結合前の変性状態の構造にも重要な意義があることが示され、天然変性蛋白質の残存構造に立脚したパーキンソン病の治療に繋がる研究である。
アルツハイマー病やパーキンソン病は、高齢化社会において極めて重要であり、本研究の残存構造の実験結果も、これからのパーキンソン病治療に社会的に大きな意義を持つ。
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