Experimental analysis of conformational evolution process of a prion by developing the kinetic NMR
| Project/Area Number |
23370068
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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 |
Biophysics
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| Research Institution | Gifu University |
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Principal Investigator |
KUWATA Kazuo 岐阜大学, 連合創薬医療情報研究科, 教授 (00170142)
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| Co-Investigator(Kenkyū-buntansha) |
KAMATARI Yuji 岐阜大学, 生命科学総合研究支援センター, 助教 (70342772)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | NMR / キネティクス / プリオン / 立体構造進化 / 活性化 |
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| Research Abstract |
In order to elucidate the conformational conversion process of a prion protein from its cellular form to the pathogenic one and the prion's evolution mechanism, we created a series of novel apparatuses, i.e. kinetic fluorescence, kinetic CD, kinetic DLS, and kinetic NMR (800 MHz). Using these novel analytical systems, we could detect the early conformational changes in a prion protein prior to the aggregation formation. Using the kinetic DLS, we detected the transient formation of disordered assembly before the stable amyloid-like aggregate formation. Using the kinetic NMR, we could detect the region specific degradation of the peptide bonds by imposing the ultrasonication. Those phenomena would give us important clues for understanding the mechanism of conformational conversion as well as that of evolution.
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] FK506reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice.2013
Author(s)
Nakagaki T, Satoh K, Ishibashi D, Fuse T, Sano K, Kamatari YO, Kuwata K, Shigematsu K, Iwamaru Y, Takenouchi T, Kitani H, Nishida N, Atarashi R.
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Journal Title
Autophagy.
Volume: 9
Issue: 9
Pages: 1386-1394
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Synthesis of an 11C-Labeled Antiprion GN8 Derivative and Evaluation of Its Brain Uptake by Positron Emission Tomography2013
Author(s)
Tsutomu Kimura, Takeo Sako, Siqin, Junji Hosokawa-Muto, Yi Long Cui, Yasuhiro Wada, Yosky Kataoka, Hisashi Doi, Suehiro Sakaguchi, Masaaki Suzuki, Yasuyoshi Watanabe, Kazuo Kuwata
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Journal Title
ChemMedChem
Volume: 8(7)
Issue: 7
Pages: 1035-1039
DOI
Related Report
Peer Reviewed
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[Journal Article] Synthesis and structure-activity relationship of 2-phenyliminochromene derivatives as inhibitors for AKR1B102013
Author(s)
Satoshi Endo, Dawei HU, Miho Suyama, Toshiyuki Matsunaga, Kenji Sugimoto, Yuji Matsuya, Ossama El-Kabbani, Kazuo Kuwata, Akira Hara, Yukio Kitade, Naoki Toyooka
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Journal Title
Bioorganic & Medicinal Chemistry
Volume: 21(21)
Issue: 21
Pages: 6378-6384
DOI
Related Report
Peer Reviewed
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[Journal Article] Anti-prion activity of an RNA aptamer and its structural basis2013
Author(s)
Mashima, T., Nishikawa, F., Kamatari Y. O., Fujiwara, H., Saimura, M., Nagata, T., Kodaki, T., Nishikawa, S., Kuwata, K., Katahira, M.
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Journal Title
Nucleic Acids Research
Volume: 41
Issue: 2
Pages: 1355-1362
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of a novel compound with antiviral activity against influenza A virus depending on PA subunit of viral RNA polymerase2012
Author(s)
Yamada K, Koyama H, Hagiwara K, Ueda A, Sasaki Y, Kanesashi SN, Ueno R, Nakamura HK, Kuwata K, Shimizu K, Suzuki M, Aida Y
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Journal Title
Microbes and infection/Institut Pasteur
Volume: 14(9)
Issue: 9
Pages: 740-747
DOI
Related Report
Peer Reviewed
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[Journal Article] 3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus2012
Author(s)
Takemura T, Urushisaki T, Fukuoka M, Hosokawa-Muto J, Hata T, Okuda Y, Hori S, Tazawa S, Araki Y, Kuwata K
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Journal Title
Evid.Based Complement.Alternat.Med.
Volume: (in press)
Pages: 1-7
DOI
Related Report
Peer Reviewed
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[Journal Article] Deciphering the Molecular Details for the Binding of the Prion Protein to Main Ganglioside GM1 of Neuronal Membranes2011
Author(s)
Sanghera N, Correia BE, Correia JR, Ludwig C, Agarwal S, Nakamura HK, Kuwata K, Samain E, Gill AC, Bonev BB, Pinheiro TJ
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Journal Title
Chemistry & biology
Volume: 18(11)
Issue: 11
Pages: 1422-31
DOI
Related Report
Peer Reviewed
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