Central Residues in Prion Protein PrPC Are Crucial for Its Conversion into the Pathogenic Isoform

• Material Type: 博士論文
• ISSN: 0021-9258
• Title: Central Residues in Prion Protein PrPC Are Crucial for Its Conversion into the Pathogenic Isoform
• Volume: 298 9
• Author/Editor: Pasiana, Agriani Dini; Miyata, Hironori; Chida, Junji; Hara, Hideyuki; Imamura, Morikazu; Atarashi, Ryuichiro; Sakaguchi, Suehiro
• Author Heading: Pasiana, Agriani Dini; Miyata, Hironori; Chida, Junji; Hara, Hideyuki; Imamura, Morikazu; Atarashi, Ryuichiro; Sakaguchi, Suehiro
• Publication, Distribution, etc.: American Society for Biochemistry and Molecular Biology|Elsevier
• Publication Date: 2022-08-13
• Publication Date (W3CDTF): 2022-08-13
• Alternative Title: 中央アミノ酸残基はプリオン蛋白質PrPCが病原性アイソフォームに変換するのに重要である; Central residues crucial for prion protein conversion
• Periodical title: Journal of Biological Chemistry
• Degree grantor/type: 徳島大学
• Date Granted: 2022-09-22
• Date Granted (W3CDTF): 2022-09-22
• Dissertation Number: 甲第3662号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3662号
• Text Language Code: eng
• Subject Heading: prion; prion disease; protein misfolding; structure-function; transgenic mice; neurodegenerative disease
• Target Audience: 一般
• Note (General): Conformational conversion of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases. However, the conversion mechanism remains to be elucidated. Here, we generated Tg(PrPΔ91-106)-8545/Prnp0/0 mice, which overexpress mouse PrP lacking residues 91-106. We showed that none of the mice became sick after intracerebral inoculation with RML, 22L, and FK-1 prion strains nor accumulated PrPScΔ91-106 in their brains except for a small amount of PrPScΔ91-106 detected in one 22L-inoculated mouse. However, they developed disease around 85 days after inoculation with bovine spongiform encephalopathy (BSE) prions with PrPScΔ91-106 in their brains. These results suggest that residues 91-106 are important for PrPC conversion into PrPSc in infection with RML, 22L, and FK-1 prions but not BSE prions. We then narrowed down the residues 91-106 by transducing various PrP deletional mutants into RML- and 22L-infected cells and identified that PrP mutants lacking residues 97-99 failed to convert into PrPSc in these cells. Our in vitro conversion assay also showed that RML, 22L, and FK-1 prions did not convert PrPΔ97-99 into PrPScΔ97-99, but BSE prions did. We further found that PrP mutants with proline residues at positions 97 to 99 or charged residues at positions 97 and 99 completely or almost completely lost their converting activity into PrPSc in RML- and 22L-infected cells. These results suggest that the structurally flexible and noncharged residues 97-99 could be important for PrPC conversion into PrPSc following infection with RML, 22L, and FK-1 prions but not BSE prions.
• DOI: info:doi/10.1016/j.jbc.2022.102381; https://doi.org/info:doi/10.1016/j.jbc.2022.102381
• Persistent ID (NDL): info:ndljp/pid/12360868; https://dl.ndl.go.jp/pid/12360868
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-11-07T16:56:35+09:00
• Format (IMT): PDF
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/117617
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp