並列タイトル等全長プリオン蛋白質の液相分離は構造変換の起因となる
タイトル（掲載誌）Journal of Biological Chemistry
授与機関名Nagasaki University (長崎大学)
一般注記Prion diseases are characterized by the accumulation of amyloid fibrils. The causative agent is an infectious amyloid that comprises solely misfolded prion protein (PrPSc). Prions can convert normal cellular prion protein (PrPC) to protease K-resistance prion protein fragment (PrP-res) in vitro; however, the intermediate steps involved in this spontaneous conversion still remain unknown. We investigated whether recombinant prion protein (rPrP) can directly convert into PrP-res via liquid–liquid phase separation (LLPS) in the absence of PrPSc. We found that rPrP underwent LLPS at the interface of the aqueous two-phase system of polyethylene glycol and dextran, whereas single-phase conditions were not inducible. Fluorescence recovery assay after photobleaching revealed that the liquid–solid phase transition occurred within a short time. The aged rPrP-gel acquired a proteinase-resistant amyloid accompanied by β-sheet conversion, as confirmed by Western blotting, Fourier transform infrared spectroscopy, and Congo red staining. The reactions required both the N-terminal region of rPrP (amino acids 23–89) and kosmotropic salts, suggesting that the kosmotropic anions may interact with the N-terminal region of rPrP to promote LLPS. Thus, structural conversion via LLPS and liquid–solid phase transition could be the intermediate steps in the conversion of prions.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1355号 学位授与年月日:令和3年6月2日
Author: Hiroya Tange, Daisuke Ishibashi, Takehiro Nakagaki, Yuzuru Taguchi, Yuji O. Kamatari, Hiroki Ozawa, Noriyuki Nishida
Citation: Journal of Biological Chemistry, 296, art. no. 100367; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-06-02)
一次資料へのリンクURLhttps://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=26968&item_no=1&attribute_id=70&file_no=1 （fulltext）
著作権情報© 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
関連情報http://hdl.handle.net/10069/00040838
関連情報（DOI）10.1016/j.jbc.2021.100367
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）