Structural studies on the cellular machineries involved in protein disulfide bond generation

2010 Fiscal Year Final Research Report

• Project/Area Number: 19687005
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Kyushu University
• Principal Investigator: INABA Kenji Kyushu University, 生体防御医学研究所, 准教授 (10423039)
• Project Period (FY): 2007 – 2010
• Keywords: ジスルフィド結合 / レドックス / 細胞品質管理 / DsbB / Ero1

Research Abstract

The formation and cleavage of disulfide bonds play a critical role in the folding into native protein structure and the elimination of misfolded proteins. Receiving the support by a Grant-in-Aid for Young Scientists (A) from MEXT, I have accomplished structural and biochemical analyses of DsbB, an E. coli membrane protein, and Ero1α, a human flavoenzyme, both of which are responsible for protein disulfide bond generation in cells. I also succeeded in the crystal structure analysis of ERdj5, a protein disulfide reductase that accelerates degradation of misfolded proteins and thereby clarified its mechanism of operation to drive the ER-associated degradation.

Research Products

• [Journal Article] Molecular basis of cyclic and specific disulfide interchange between human Ero1α and PDI (2011)
  • Author(s): Masui, S., Vavassori, S., Fagioli, C., Sitia, R., Inaba, K.
  • Journal Title: J.Biol.Chem. 286 Pages: 16261-16271
  • Peer Reviewed
• [Journal Article] Structural basis of an ERAD pathway mediated by the ER-resident disulfide reductase ERdj5 (2011)
  • Author(s): Hagiwara, M., Maegawa, K., Suzuki, M., Ushioda, R., Araki, K., Matsimoto, Y., Hoseki, J., Nagata, K., Inaba, K.
  • Journal Title: Mol.Cell 41 Pages: 432-444
  • Peer Reviewed
• [Journal Article] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization (2011)
  • Author(s): Ishitani, S., Inaba, K., Matsumoto, K., Ishitani, T.
  • Journal Title: Mol.Biol.Cell 22 Pages: 266-277
  • Peer Reviewed
• [Journal Article] 小胞体品質管理を支えるジスルフィド結合形成・開裂因子の構造基盤 (2011)
  • Author(s): 稲葉謙次
  • Journal Title: 生体機能関連化学ニュースレター Vol.25 Pages: 3-6
• [Journal Article] Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI (2010)
  • Author(s): Inaba, K., Masui, S., Iida, H., Vavassori, S., Sitia, R., Suzuki, M.
  • Journal Title: EMBO J. 29 Pages: 3330-3343
  • Peer Reviewed
• [Journal Article] Structural basis of protein disulfide bond generation in the cell (2010)
  • Author(s): Inaba, K.
  • Journal Title: Genes to Cells 15 Pages: 935-943
  • Peer Reviewed
• [Journal Article] Redox-dependent intramolecular domain rearrangement of protein disulfide isomerase coupled with exposure of its substrate-binding hydrophobic surface. (2010)
  • Author(s): Serve, O., Kamiya, Y., Maeno, A., Nakano, M., Murakami, C., Sasakawa, H., Yamaguchi, Y., Harada, T., Kurimoto, E., Yagi-Utsumi, M., Iguchi, T., Inaba, K., Kikuchi, J., Asami, O., Kajino, T., Oka, T., Nakasako, M., Kato, K.
  • Journal Title: J.Mol.Biol. 396 Pages: 361-374
  • Peer Reviewed
• [Journal Article] Dynamic nature of disulfide bond formation catalysts revealed by crystal structures of DsbB (2009)
  • Author(s): Inaba, K., Murakami, S., Nakagawa, A., Iida, H., Kinjo, M., Ito, K., Suzuki, M.
  • Journal Title: EMBO J 28 Pages: 779-791
  • Peer Reviewed
• [Journal Article] Disulfide bond formation system in Eschericia coli (2009)
  • Author(s): Inaba, K.
  • Journal Title: J.Biochem. 146 Pages: 591-597
  • Peer Reviewed
• [Journal Article] DsbBの結晶構造が解かれるまでー臥薪嘗胆、初志貫徹 (2009)
  • Author(s): 稲葉謙次
  • Journal Title: 実験医学(羊土社) Vol.26 Pages: 945-948
• [Journal Article] 大腸菌におけるDsbB-DsbA タンパク質ジスルフィド結合形成システムの構造と機能発現メカニズム (2009)
  • Author(s): 稲葉謙次
  • Journal Title: 日本結晶学会誌 第51巻 Pages: 100-103
• [Journal Article] A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of E.coli (2008)
  • Author(s): Inaba, K., Suzuki, M., Maegawa, K., Akiyama, S., Ito, K., Akiyama, Y.
  • Journal Title: J.Biol.Chem. 283 Pages: 35042-35052
  • Peer Reviewed
• [Journal Article] The disulfide bond formation (Dsb) system (2008)
  • Author(s): Ito, K., Inaba, K.
  • Journal Title: Curr.Opin.Struct.Biol. 18 Pages: 450-458
  • Peer Reviewed
• [Journal Article] Protein disulfide bond generation in Escherichia coli DsbB-DsbA (2008)
  • Author(s): Inaba, K.
  • Journal Title: J.Synchr.Rad. 15 Pages: 199-201
  • Peer Reviewed
• [Journal Article] Structure and mechanisms of the DsbB-DsbA disulfide bond generation machine (2008)
  • Author(s): Inaba, K., Ito, K.
  • Journal Title: Biochem.Biophys.Acta.Molecular Cell Research 1783 Pages: 520-529
  • Peer Reviewed
• [Journal Article] 構造が明らかにしたジスルフィド結合の形成機構 (2007)
  • Author(s): 稲葉謙次、伊藤維昭
  • Journal Title: 蛋白質核酸酵素、共立出版 Vol.52 Pages: 853-861
• [Journal Article] タンパク質ジスルフィド結合の形成に関わる酵素群-構造が明らかにしたそのメカニズム (2007)
  • Author(s): 稲葉謙次
  • Journal Title: 酵素工学ニュース、日本酵素工学会 Vol.57 Pages: 17-23
• [Journal Article] ジスルフィド結合の形成メカニズム (2007)
  • Author(s): 伊藤維昭、稲葉謙次
  • Journal Title: Medical Bio、オーム社 Vol.4 Pages: 58-65
• [Journal Article] 細胞内に張り巡らされた蛋白質ジスルフィドネットワーク (2007)
  • Author(s): 稲葉謙次、伊藤維昭
  • Journal Title: 蛋白質の一生 集中マスター、羊土社 Pages: 77-85
• [Journal Article] 小胞体に内在するジスルフィド還元酵素ERdj5により促進される小胞体関連分解経路の構造的な基盤
  • Author(s): 萩原誠智、永田和宏、稲葉謙次
  • Journal Title: 新着論文ニュースレター
  • URL: http://first.lifesciencedb.jp/archives/2403#more-2403)
• [Presentation] Convergent evolution of the protein disulfide bond formation systems in the biological kingdoms (2010)
  • Author(s): 稲葉謙次
  • Organizer: BMB2010
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 20101207-20101210
• [Presentation] Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5 (2010)
  • Author(s): Inaba, K.
  • Organizer: The 10th conference of the Asian Crystallographic Association
  • Place of Presentation: Busan, Korea(invited)
  • Year and Date: 20101031-20101103
• [Presentation] Structural basis of regulated protein disulfide bond formation in human cells (2010)
  • Author(s): Inaba, K.
  • Organizer: The 3rd international symposium on protein community
  • Place of Presentation: Nara, Japan(invited)
  • Year and Date: 20100913-20100916
• [Presentation] Structures of mammalian Ero1a and ERdj5 (2010)
  • Author(s): Inaba, K.
  • Organizer: Gordon Reserch Conference on thiol-based redox regulation & signaling
  • Place of Presentation: Lucca, Italy(invited)
  • Year and Date: 20100509-20100514
• [Presentation] 細胞品質管理に関わるタンパク質ジスルフィド結合形成・開裂因子の構造的基盤の確立 (2009)
  • Author(s): 稲葉謙次
  • Organizer: 第32回日本分子生物学会年会 第7回日本分子生物学会三菱化学奨励賞受賞記念講演会
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2009-12-11
• [Presentation] Structure and mechanism of the DsbB-DsbA protein disulfide generation system in E.coli (2008)
  • Author(s): Inaba, K.
  • Organizer: XXI Congress and General Assembly of the International union of Crystallography
  • Place of Presentation: Osaka, Japan(invited)
  • Year and Date: 20080823-20080830
• [Presentation] Structural basis for protein disulfide generation in the cell (2008)
  • Author(s): Inaba, K.
  • Organizer: Gordon conference on thiol-based redox regulation & signaling
  • Place of Presentation: Lucca, Italy(invited)
  • Year and Date: 20080525-20080530
• [Presentation] Structural basis of the DsbA-DsbB-UQ oxidative system in E.coli. (2007)
  • Author(s): Inaba, K.
  • Organizer: Boden Conference on disulfide bonds and their role in protein folding and function
  • Place of Presentation: Queensland, Australia(invited)
  • Year and Date: 20070729-20070802
• [Book] ジスルフィド結合、チオレドキシンフォールド、Dsb蛋白質 キーワード:蛋白質の一生 Vol.53 (2008)
  • Author(s): 稲葉謙次
  • Total Pages: 940,969,1043
  • Publisher: 共立出版
• [Book] 細胞内に張り巡らされた蛋白質ジスルフィドネットワーク 蛋白質の一生 集中マスター (2007)
  • Author(s): 稲葉謙次、伊藤維昭
  • Total Pages: 77-85
  • Publisher: 羊土社
• [Book] Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation. (2007)
  • Author(s): Inaba, K., Ito, K.
  • Total Pages: 16-17
  • Publisher: Spring 8 Research Frontier 2006
• [Book] The Structural and Chemical Basis of Protein Disulfide Bond Formation in E.coli (2007)
  • Author(s): Inaba, K.
  • Total Pages: 42-43
  • Publisher: KEK Highlight 2006
• [Remarks] ホームページ
  • URL: http://www.bioreg.kyushu-u.ac.jp/labo/pgpc/