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Elucidation of the mechanism of peptidyl-tRNA hydrolysis in the stalled eukaryotic ribosome

Research Project

Project/Area Number 18K06080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionNiigata University

Principal Investigator

Ito Kosuke  新潟大学, 自然科学系, 准教授 (20502397)

Co-Investigator(Kenkyū-buntansha) 西川 周一  新潟大学, 自然科学系, 教授 (10252222)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords翻訳 / ペプチジルtRNA / 分子遺伝学的解析 / X線結晶構造解析 / ユビキチン化タンパク質運搬因子 / リボソーム / 真核生物
Outline of Final Research Achievements

During the course of protein synthesis, ribosomes occasionally stall due to various reasons and thus produce peptidyl-tRNAs, which are immature translation products. This unfavorable situation is solved by hydrolyzing the peptidyl-tRNA into the peptide and tRNA components. However, the mechanism of the peptidyl-tRNA hydrolysis in the stalled ribosome still remains unclear in eukaryotes. Our study revealed that Vms1 is not sufficient to hydrolyze the peptidyl-tRNA in the stalled ribosome. We also clarified the structural basis of the substrate recognition and the hydrolysis reaction of Pth, which acts in the cytosol to hydrolyze the peptidyl-tRNAs.

Academic Significance and Societal Importance of the Research Achievements

翻訳の品質管理機構の不全はアルツハイマー病やパーキンソン病などの神経変性疾患を引き起こす。そのため、本研究成果はそれら病気の治療法の開発に繋がるものである。一方、抗生物質の開発研究においては、Pthが新規ターゲットタンパク質として注目されているが、今回我々がPthの基質認識や活性発現の構造基盤を明らかにしたことにより、Pthをターゲットにした薬剤の開発研究が加速することになる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2021 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results)

  • [Journal Article] High-resolution crystal structure of peptidyl-tRNA hydrolase from Thermus thermophiles2019

    • Author(s)
      Matsumoto A., Uehara Y., Shimizu Y., Ueda T., Uchiumi T., Ito K.
    • Journal Title

      Proteins

      Volume: 87 Issue: 3 Pages: 226-235

    • DOI

      10.1002/prot.25643

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ペプチジルtRNA加水分解酵素Pth2-tRNA複合体の構造解析2021

    • Author(s)
      茅原真晃, 今井大達, 内海 利男, 伊東 孝祐
    • Organizer
      第15回無細胞生命科学研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ペプチジルtRNA加水分解酵素Pth2の構造・機能解析2019

    • Author(s)
      茅原真晃、中筋航、上原祐二、内海利男、伊東孝祐
    • Organizer
      第60回新潟生化学懇話会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペプチジルtRNA加水分解酵素Pth2の構造・機能解析2019

    • Author(s)
      茅原真晃、中筋航、上原祐二、市邨晃久、今井大逹、内海利男、伊東孝祐
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペプチジルtRNA加水分解酵素・プロテアソーム輸送タンパク質複合体のX線結晶構造解析2018

    • Author(s)
      市邨晃久、笠原杏子、今井大達、上原祐二、西川周一、内海利男、伊東孝祐
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ペプチジルtRNA加水分解酵素Pth2の構造・機能解析2018

    • Author(s)
      茅原真晃、中筋航、上原祐二、内海利男、伊東孝祐
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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