The role of an unstructured region in the proteasome inhibition

• Project/Area Number: 22770137
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: University of Toyama (2011); The Institute of Physical and Chemical Research (2010)
• Principal Investigator: INOBE Tomonao 富山大学, 先端ライフサイエンス拠点, 特命助教 (50568855)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 細胞内タンパク質分解 / プロテアソーム / ポリグルタミン病 / 神経変性疾患 / 天然変性蛋白質 / 蛋白質 / 分解 / ハンチントン病 / ハンチンチン / 蛋白質分解 / 天然変性領域

Research Abstract

We have investigated how the misfolded proteins in various neurodegenerative diseases inhibit the protein degradation by the proteasome. We found that an unstructured region of the misfolded protein directly interacts with the proteasome, which causes the competitive inhibition of the degradation of natural proteasome substrates and the disassembly of the 19S proteasome complex.

Research Products

• [Journal Article] Sequence-and Species-Dependence of Proteasomal Processivity (2012)
  • Author(s): Kraut, DA., Israeli, E., Schrader, E., Patil, A., Nakai, K., Nanavati, D., Inobe, T. and Matouschek, A.
  • Journal Title: ACS Chem. Biol.(in press)
  • Peer Reviewed
• [Journal Article] 変性領域を介したプロテアソームの基質認識機構 (2011)
  • Author(s): 伊野部智由
  • Journal Title: 生物物理 Volume: 51 Pages: 276-277
  • NAID: 10030038026
  • Peer Reviewed
• [Journal Article] プロテアソームによるタンパク質分解に必要な分解シグナルの配置 (2011)
  • Author(s): 伊野部智由
  • Journal Title: 実験医学 Volume: 29 Pages: 2135-2138
• [Journal Article] Dissecting a biomolecular process of MgATP2-binding to the chaperonin GroEL (2011)
  • Author(s): Chen, J., Makabe, K., Nakamura, T., Inobe, T. and Kuwajima, K.
  • Journal Title: J. Mol. Biol Volume: 410 Pages: 343-356
  • Peer Reviewed
• [Journal Article] Defining the Geometry of the Two-component Proteasome Degron (2011)
  • Author(s): Inobe, T., Fishbain, S., Prakash, S. and Matouschek, A.
  • Journal Title: Nature Chem. Biol Volume: 7 Pages: 161-167
  • Peer Reviewed
• [Journal Article] Dissecting a biomolecular process of MgATP^<2-> binding to the chaperonin GroEL (2011)
  • Author(s): Chen, J., Makabe, K., Nakamura, T., Inobe, T., Kuwajima, K.
  • Journal Title: Journal of Molecular Biology Volume: 410 Issue: 2 Pages: 343-356
  • DOI: 10.1016/j.jmb.2011.05.018
  • Peer Reviewed
• [Journal Article] Defining the geometry of the two-component proteasome degron (2011)
  • Author(s): Tomonao Inobe
  • Journal Title: Nature Chemical Biology Volume: 7 Pages: 161-167
  • Peer Reviewed
• [Journal Article] 蛋白質分解系活性化による神経変性疾患治療 (2010)
  • Author(s): 伊野部智由、貫名信行
  • Journal Title: 実験医学 Volume: 28 Pages: 788-794
• [Presentation] Fluctuation-mediated substrate recognition by the proteasome (2012)
  • Author(s): Inobe, T. and Takahashi, K.
  • Organizer: The 5th International Symposium on Molecular Science of Fluctuations toward Biological Functions
  • Place of Presentation: Nara, Japan
• [Presentation] プロテアソームによる蛋白質アンフォールディングと分解:その初期過程 (2011)
  • Author(s): 伊野部智由
  • Organizer: 日本物理学会2011年秋季大会
  • Place of Presentation: 富山大学
• [Presentation] Defining the geometry of the two-component proteasome degron (2010)
  • Author(s): Inobe, T., Fishbain, S., Prakash, S., and Matouschek, A.
  • Organizer: 48th Annual Meeting of the Biophysical Society of Japan
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2010-09-20
• [Presentation] Defining the geometry of the two-component proteasome degron (2010)
  • Author(s): Tomonao Inobe
  • Organizer: 48th Annual meeting of the Biophysical society of Japan
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-20
• [Presentation] 生体内蛋白質アンフォールディングの分子機構 (2010)
  • Author(s): 伊野部智由
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-17
• [Presentation] Molecular mechanism of protein unfolding in the cell (2010)
  • Author(s): Inobe, T., Fishbain, S., Prakash, S. and Matouschek, A.
  • Organizer: The 10th Annual Meeting of The Protein Science Society of Japan
  • Place of Presentation: Sapporo, Japan
• [Presentation] プロテアソームによる蛋白質アンフォールディングと分解:その初期過程
  • Author(s): 伊野部智由
  • Organizer: 日本物理学会
  • Place of Presentation: 富山大学
• [Remarks]
  • URL: http://inobelab.wordpress.com/