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Instability of familial spongiform encephalopathy-related prion mutants

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Title: Instability of familial spongiform encephalopathy-related prion mutants
Authors: Watanabe, Yasuko Browse this author
Hiraoka, Wakako Browse this author
Shimoyama, Yuhei Browse this author
Horiuchi, Motohiro Browse this author →KAKEN DB
Kuwabara, Mikinori Browse this author
Inanami, Osamu Browse this author →KAKEN DB
Keywords: prion protein
salt bridge
conformational stability
histidine residue
familial spongiform encephalopathy
conformational transition
Issue Date: 1-Feb-2008
Journal Title: Biochemical and Biophysical Research Communications
Volume: 366
Issue: 1
Start Page: 244
End Page: 249
Publisher DOI: 10.1016/j.bbrc.2007.11.145
PMID: 18062918
Abstract: We examined the influence of D177N (D178N in humans) mutation on the conformational stability of the S2 region of moPrPC with varying pHs by using the SDSL-ESR technique. 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 to pH 4.0. Our results suggested that the disappearance of a salt bridge (D177-R163) induced the increase in the instability of S2 region. Moreover, the line shape of the ESR spectrum obtained from H176S neighboring the salt bridge linked to the S2 region was similar to D177N. These results indicate that the protonation of H176 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 PrPSc structure in hereditary prion disease.
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 稲波 修

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