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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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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 / αシヌクレイン / 変異体 / アミロイド / 折り畳み / オリゴマー / 蛋白質間相互作用 / 変性 / 折りたたみ / 蛋白質 / 高分子構造・物性 / 生物物理 / 分子認識 / 超分子化学 |
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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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| 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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Report
(5 results)
Research Products
(21 results)
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[Journal Article] Distinct residual and disordered structures of alpha-synuclein analyzed by amide-proton exchange and NMR signal intensity2020
Author(s)
Okuwaki, R., Shinmura, I., Morita, S., Matsugami, A., Hayashi, F., Goto, Y., Nishimura, C.
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Journal Title
Biochimica et Biophysica Acta-Proteins and Proteomics
Volume: 1868
Issue: 9
Pages: 140464-140464
DOI
Related Report
Peer Reviewed
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[Journal Article] Non-native alpha-helices in the initial folding intermediate facilitate the ordered assembly of the beta-barrel in beta-lactoglobulin2017
Author(s)
Sakurai, K., Yagi, M., Konuma, T., Takahashi, S., Nishimura, C., Goto, Y.
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Journal Title
Biochemistry
Volume: 56
Issue: 36
Pages: 4799-4807
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of Glu12-His89 interaction on dynamic structures in HIV-1 p17 matrix protein elucidated by NMR2016
Author(s)
Konagaya, Y., Miyakawa, R., Sato, M., Matsugami, A., Watanabe, S., Hayashi, F., Kigawa, T., and Nishimura, C.
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Journal Title
PLoS One
Volume: 11
Issue: 12
Pages: e0167176-e0167176
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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