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

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Niigata 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
• 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

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.

Free Research Field

構造生物化学

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。