C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers.

• Material Type: 博士論文
• Title: C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers.
• Author/Editor: Nanaura, Hitoki; Kawamukai, Honoka; Fujiwara, Ayano; Uehara, Takeru; Aiba, Yuichiro; Nakanishi, Mari; Shiota, Tomo; Hibino, Masaki; Wiriyasermkul, Pattama; Kikuchi, Sotaro; Nagata, Riko; Matsubayashi, Masaya; Shinkai, Yoichi; Niwa, Tatsuya; Mannen, Taro; Morikawa, Naritaka; Iguchi, Naohiko; Kiriyama, Takao; Morishima, Ken; Inoue, Rintaro; Sugiyama, Masaaki; Oda, Takashi; Kodera, Noriyuki; Toma-Fukai, Sachiko; Sato, Mamoru; Taguchi, Hideki; Nagamori, Shushi; Shoji, Osami; Ishimori, Koichiro; Matsumura, Hiroyoshi; Sugie, Kazuma; Saio, Tomohide; Yoshizawa, Takuya; Mori, Eiichiro
• Author Heading: Nanaura, Hitoki; Kawamukai, Honoka; Fujiwara, Ayano; Uehara, Takeru; Aiba, Yuichiro; Nakanishi, Mari; Shiota, Tomo; Hibino, Masaki; Wiriyasermkul, Pattama; Kikuchi, Sotaro; Nagata, Riko; Matsubayashi, Masaya; Shinkai, Yoichi; Niwa, Tatsuya; Mannen, Taro; Morikawa, Naritaka; Iguchi, Naohiko; Kiriyama, Takao; Morishima, Ken; Inoue, Rintaro; Sugiyama, Masaaki; Oda, Takashi; Kodera, Noriyuki; Toma-Fukai, Sachiko; Sato, Mamoru; Taguchi, Hideki; Nagamori, Shushi; Shoji, Osami; Ishimori, Koichiro; Matsumura, Hiroyoshi; Sugie, Kazuma; Saio, Tomohide; Yoshizawa, Takuya; Mori, Eiichiro
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2021-09-06
• Publication Date (W3CDTF): 2021-09-06
• Alternative Title: C9orf72リピート異常伸長より生じる毒性ペプチドは相分離制御因子の機能を阻害する
• Periodical title: Nature communications
• No. or year of volume/issue: 12 1
• Volume: 12
• Issue: 1
• Pages: Article No.5301-
• ISSN (Periodical Title): ISSN : 2041-1723
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2022-03-15
• Dissertation Number: 甲第826号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Biophysical chemistry; Intrinsically disordered proteins; Neurodegeneration
• Target Audience: 一般
• Note (General): type:Thesis; Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration.; 博士（医学）・甲第826号・令和4年3月15日; © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.; identifier:Nature communications Vol.12 No.1 Article No.5301 (2021 Sep); identifier:20411723; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4009; identifier:Nature communications, 12(1): Article No.5301
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4009/1/01%e7%94%b2826%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4009/2/02%e7%94%b2826%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4009/3/03%e7%94%b2826%e6%9c%ac%e6%96%87.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4009/4/04%e7%94%b2826Suppl..pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1038/s41467-021-25560-0
• Periodical Title (NCID): AA12645905; https://ci.nii.ac.jp/ncid/AA12645905
• Data Provider (Database): 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）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU