Structural basis for catalytic mechanism of ubiquitin ligase Parkin

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16068
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kyoto University (2020); The University of Tokyo (2019)
• Principal Investigator: Okatsu Kei 京都大学, 理学研究科, 助教 (00739641)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ユビキチン化 / リン酸化 / パーキンソン病 / ミトコンドリア / オートファジー

Outline of Final Research Achievements

Parkin is a ubiquitin ligase E3 that is activated on mitochondria at reduced membrane potential to catalyze the ubiquitination of mitochondrial outer membrane proteins. However, the catalytic mechanism remains unclear. In this study, we identified the minimal region required for E3 activity of Parkin. The E2 required for the E3 activity of Parkin was identified by the screening of recombinant E2. Furthermore, we searched for residues important for catalysis based on the structural information of E2 and the catalytic domain of Parkin. Thus, we have obtained an understanding of the catalytic mechanism based on biochemical experiments and steric structure.

Free Research Field

生命科学

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病は高齢になるほど発症確立が高くなるので、高齢化社会において原因遺伝産物の機能を理解することは重要である。Parkinは若年性パーキンソン病の原因遺伝子産物であり、酵素活性がその機能に重要であることが知られている。本研究では、E2の認識や活性中心とユビキチン鎖の関係を生化学実験や立体構造に基づいて理解した。