生体分子構造 分野
細胞内には、タンパク質の品質を管理するための巧妙な仕組みが備わっています。当研究室では、細胞が有するタンパク質の立体構造形成補助システムと不良品タンパク質を速やかに分解除去するシステムについて、構造生物学・生化学・プロテオミクス・細胞生物学的手法を駆使し、徹底的に解明することを目指しています。本研究課題を遂行することにより、細胞内で蓄積するミスフォールドタンパク質が引き起こす種々の病態の分子レベルでの成因解明につながることも期待されます。
特色・実績
上記の研究に関し、以下の代表的論文を発表しています。
- Inoue, M., Sakuta, N., Watanabe, S., Zhang, Y., Yoshikaie, K., Tanaka, Y., Ushioda, R., Kato, Y., Takagi, J., Tsukazaki, T., Nagata, K. and Inaba, K.* “Structural basis of sarco/endoplasmic reticulum Ca2+-ATPase 2b regulation via transmembrane helix interplay” Cell Reports, 27, 1221-1230 (2019)
- Okumura, M.*, Noi, K., Kanemura, S., Kinoshita, M., Saio, T., Inoue, Y., Hikima, T., Akiyama, S., Ogura, T.* and Inaba, K.* “Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding” Nature Chemical Biology 15, 499-509 (2019)
- Watanabe S., Amagai Y., Sannino S., Tempio T., Anelli T., Harayama M., Masui S., Sorrentino I., Yamada M., Sitia R*, and Inaba K*. “Zinc regulates ERp44-dependent protein quality control in the early secretory pathway.” Nature Communications, 10, 603 (2019)
- Watanabe, S., Harayama, M., Kanemura, S., Sitia, R. and Inaba, K.* “Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface” Proc Natl Acad Sci U S A. 114, 3224-3232 (2017)
- Maegawa, K., Watanabe, S., Noi, K., Okumura, M., Amagai, Y., Inoue, M., Ushioda, R., Nagata, K., Ogura, T. and Inaba, K.* “The highly dynamic nature of ERdj5 is key to efficient elimination of aberrant protein oligomers through ER-associated degradation” Structure, 25, 846-857(2017)
- Arai, K., Takei, T., Okumura, M., Watanabe, S., Amagai, Y., Asahina, Y., Moroder, L., Hojo, H.*, Inaba, K.* and Iwaoka, M.* “Preparation of selenoinsulin as a long-lasting insulin analog” Angewandte Chemie 56, 5522-5526 (2017)
- Ushioda R, Miyamoto A, Inoue M, Watanabe S, Okumura M, Maegawa KI, Uegaki K, Fujii S, Fukuda Y, Umitsu M, Takagi J, Inaba K., Mikoshiba K, Nagata K. “Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by disulfide reductase ERdj5.” Proc Natl Acad Sci U S A. 113(41):E6055-E6063 (2016)
- Kojima, R., Okumura, M., Masui, S., Kanemura, S., Inoue, M., Saiki, M., Yamaguchi, H., Hikima, T., Suzuki, M., Akiyama, S. and Inaba, K.* “Radically different thioredoxin domain arrangement of ERp46, an efficient disulfide-bond introducer of the mammalian PDI family”, Structure, 22, 431-443 (2014)
- Vavassori, S., Cortini, M., Masui, S. Sannino, S., Anelli, T., Caserta, I. R., Fagioli, C., Fornili, A., Mossuto, M. F., Degano, M, Inaba, K. and Sitia, R.* “A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly” Mol. Cell 50, 783-792 (2013)
- Hagiwara, M., Maegawa, K., Suzuki, M. †, Ushioda, R., Araki, K., Matsimoto, Y., Hoseki, J., Nagata, K.* and Inaba, K.* “Structural basis of an ERAD pathway mediated by the ER-resident disulfide reductasse ERdj5” Mol. Cell 41, 432-444 (2011)
- Inaba, K.*, Masui, S., Iida, H. Vavassori, S., Sitia, R. and Suzuki, M. “Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI” EMBO J 29, 3330-3343 (2010)
- Inaba, K.*, Murakami, S., Nakagawa, A., Iida, H., Kinjo, M., Ito, K. and Suzuki, M. “Dynamic nature of disulfide bond formation catalysts revealed by crystal structures of DsbB” EMBO J 28, 779-791 (2009)
- Inaba, K.*, Murakami, S., Suzuki, M., Nakagawa, A., Yamashita, E., Okada, K. and Ito, K.* “Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation” Cell 127, 789-801 (2006)
- Inaba, K., Takahashi, Y. -H., Ito, K. and Hayashi, S. “Critical role of a thiolate-quinone charge transfer complex and its adduct form in de novo disulfide bond generation by DsbB” Proc. Natl. Acad. Sci. USA. 103, 287-292 (2006)
- Inaba, K. and Ito, K. “Paradoxical redox properties of DsbB and DsbA in the protein disulfide-introducing reaction cascade” EMBO J 21, 2646-2654 (2002)
| 研究室URL | http://www.tagen.tohoku.ac.jp/labo/inaba/ |
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教員紹介
教授 稲葉 謙次
詳細を見る
- 細胞におけるタンパク質品質管理システムの分子構造レベルでの解明
- 小胞体におけるジスルフィド結合形成ネットワークの網羅的解析
- 細胞オルガネラにおける金属イオン濃度恒常性維持機構の解明
