2006 Fiscal Year Final Research Report Summary
Structural analysis of prion proteins and mechanism of PrPsc transition by using a novel dynamic molecular structure analysis
| Project/Area Number |
17380178
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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 |
Applied veterinary science
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| Research Institution | Hokkaido University |
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Principal Investigator |
INANAMI Osamu Hokkaido University, Graduate School of Veterinary Medicine, Associate Professor, 大学院獣医学研究科, 助教授 (10193559)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Motohiro Hokkaido University, Graduate School of Veterinary Medicine, Professor, 大学院獣医学研究科, 教授 (30219216)
KARIWA Hiroaki Hokkaido University, Graduate School of Veterinary Medicine, Associate Professor, 大学院獣医学研究科, 助教授 (70224714)
INABA Mustumi Hokkaido University, Graduate School of Veterinary Medicine, Professor, 大学院獣医学研究科, 教授 (00183179)
KUWABARA Mikinori Hokkaido University, Graduate School of Veterinary Medicine, Professor, 大学院獣医学研究科, 教授 (10002081)
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| Project Period (FY) |
2005 – 2006
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| Keywords | prion / Creutzfeldt-Jacob disease (CJD), / bovine spongiformencephalopathy (BSE) / site-directed spin labeling (SDSL) / nitroxide spin probe / electron spin resonance (ESR) / 3D structure / Structural biology |
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| Research Abstract |
We examined the influence of D177N (178N in humans) mutation on the conformational stability of the S2 region of moPrPc with varying pHs by using the SDSL-ESR technique. We prepared moPrPc mutants that reacted with methane thiosulfonate spin-probes (Y161R1 and Y161R1/D177N). The ESR spectrum of D177N at pH 7.5 was narrower than that of Y161R1, referred to as WT^*. The ESR spectrum of D177N did not change when pH in the solution decreased from 7.5 to 4.0.These results suggested that the disappearance of a salt bridge (D177-R163) induced the increase in the instability of S2 region. The values of 1/ H of the central component (Mi=0) in the ESR spectrum obtained from WT^* remained constant from pH 7.5 to pH 6.5, whereas an abrupt increase of 1/Ho occurred when the pH in the solution decreased to under 6.0. These findings indicated that the conformational transition from a rigid structure to a flexible structure existed at between pH 6.5 and pH 6.0. Moreover, the line shape of the ESR spectrum obtained from H176S neighboring the salt bridge linked to the S2 region was narrower than that of WT^* at pH 7.5. When the pH in the solution decreased from 7.5 to 4.0, the change in the spectrum of H176S was small. These results indicate that the protonation of H 176 is strongly associated with the stability of S2 region. These findings are important for understanding the mechanism by which the disruption of the salt bridge in the S2 region forms the pathogenic PrP_Sc structure in hereditary Creutzfeldt-Jacob disease and fatal familial insomnia.
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Author(s)
Yasui, H., Inanami, O., Asanuma, T., Iizuka, D., Nakajima, T., Kon, Y., Matsuda, A., Kuwabara, M.
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Journal Title
Internatinal Journal of Radiation Oncology, Biology,Physics (印刷中)
Description
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[Journal Article] Reactive oxygen species mediate shear stress-induced fluid-phase endocytosis in vascular endothelial cells.2006
Author(s)
Niwa, K., Sakai, J., Karino, T., Aonuma, H., Watanabe, T., Ohyama, T., Inanami, O., Kuwabara, M.
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Journal Title
Free Radical Research. 40(4)
Pages: 359-367
Description
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[Journal Article] Synthesis and Characterization of a Practically Useful DEPMPO-type Spin Trap, 5-(2,2-Dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1- pyrroline N-oxide (CYPMPO).2006
Author(s)
Kamibayashi M, Oowada S, Kameda H, Okada T, Inanami O, Ohta S, Ozawa T, Makino K, Koyake Y
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Journal Title
Free Radical Research. 40(11)
Pages: 1166-1172
Description
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