| Project/Area Number |
15370047
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Tottori University |
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Principal Investigator |
KAWATA Yasushi Tottori University, Faculty of Engineering, Professor, 工学部, 教授 (40177697)
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| Co-Investigator(Kenkyū-buntansha) |
MIZOBATA Tomohiro Tottori University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (50263489)
HONGO Kunihiro Tottori University, Faculty of Engineering, Associate Professor, 工学部, 助手 (80335504)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | Amyloid fibril / Oligomeric protein / α-synuclein / Molecular chaperone / Molecular compactness / Functional mechanism / Chaperonin / Neurodegenerative disease / GroES / コンフォメーション病 / 構造変化 / 構造安定性 / 蛋白質の構造安定性 / コンフォメーション変化 / アミロイド線維形成 / シャペロニンGroES |
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| Research Abstract |
Studies on protein stability including global conformational changes and functional mechanism of molecular chaperone, which are closely related to biofunction and diseases, were performed in detail and following results were obtained.
1.Study on structure and stability of oligomeric protein : We have determined X-ray crystal structure of thermostable aspartase enzyme, and elucidated the mechanism of thermostability and active site structure of the enzyme comprising from 4 identical subunits. On the other hand, we studied solution structure and molecular unfolding mechanism of E.coli co-chaperonin GroES heptamer at high protein concentrations by using small angle X-ray scattering.
2.Study on conformational changes and amyloid fibril formation of protein : We have found that oligomeric protein GroES, that is a non-related protein to disease, formed a typical amyloid fibril under a certain condition, and elucidated the fibril formation mechanism in terms of molecular compactness. Furthermore, we studied fibril formation mechanism of α-synuclein, a causative protein of Parkinson disease, and proved that the amyloid fibril formation of α-synuclein is accelerated markedly in the presence of preformed seeds of other different protein's fibrils.
3.Study on structure and function of molecular chaperone : We have studied in detail structure and function relationship of group I chaperonin GroEL from E.coli and group II chaperonins from hyper-thermostable strains. We have found that domain movements of GroEL are very important for the function and that cobalt and manganese ions are novel factors for nucleotide hydrolysis activity and substrate refolding function of group II chaperonin. Furthermore, we have investigated function of zebrafish Hsp60, and elucidated that Hsp60 is required for blastema formation and maintenance during regeneration.
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