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タイトル
和文:C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers. 
英文:C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers. 
著者
和文: Hitoki Nanaura, Kawamukai H, Fujiwara A, Uehara T, Yuichiro Aiba, Nakanishi M, Shiota T, Hibino M, Pattama Wiriyasermkul, Kikuchi S, Riko Nagata, Masaya Matsubayashi, Yoichi Shinkai, 丹羽達也, Taro Mannen, Naritaka Morikawa, Iguchi N, Takao Kiriyama, Ken Morishima, Inoue R, Masaaki Sugiyama, Oda T, Kodera N, Toma-Fukai S, Sato M, Hideki Taguchi, Shushi Nagamori, Osami Shoji, Koichiro Ishimori, Hiroyoshi Matsumura, Sugie K, Tomohide Saio, Yoshizawa T, Eiichiro Mori.  
英文: Hitoki Nanaura, Kawamukai H, Fujiwara A, Uehara T, Yuichiro Aiba, Nakanishi M, Shiota T, Hibino M, Pattama Wiriyasermkul, Kikuchi S, Riko Nagata, Masaya Matsubayashi, Yoichi Shinkai, Tatsuya Niwa, Taro Mannen, Naritaka Morikawa, Iguchi N, Takao Kiriyama, Ken Morishima, Inoue R, Masaaki Sugiyama, Oda T, Kodera N, Toma-Fukai S, Sato M, Hideki Taguchi, Shushi Nagamori, Osami Shoji, Koichiro Ishimori, Hiroyoshi Matsumura, Sugie K, Tomohide Saio, Yoshizawa T, Eiichiro Mori.  
言語 English 
掲載誌/書名
和文:Nature communications 
英文:Nature communications 
巻, 号, ページ        
出版年月 2021年9月6日 
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英文: 
会議名称
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英文: 
公式リンク https://europepmc.org/articles/PMC8421406
 
DOI https://doi.org/10.1038/s41467-021-25560-0
アブストラクト 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.

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