Elucidation of the mechanism of peptidyl-tRNA hydrolysis in the stalled eukaryotic ribosome
| Project/Area Number |
18K06080
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43020:Structural biochemistry-related
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| Research Institution | Niigata University |
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Principal Investigator |
Ito Kosuke 新潟大学, 自然科学系, 准教授 (20502397)
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| Co-Investigator(Kenkyū-buntansha) |
西川 周一 新潟大学, 自然科学系, 教授 (10252222)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(6 results)
