Regulatory mechanism of pH- and nucleic acid-dependent K63Ub chain elongation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06496
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: National Institute of Genetics
• Principal Investigator: Kurokawa Yumiko 国立遺伝学研究所, 新分野創造センター, 特任研究員 (10381633)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ユビキチン / DNA / RNA / K63 / pH / Ubc13 / Mms2 / 高速AFM

Outline of Final Research Achievements

The molecular mechanisms of K63Ub chain formation and elongation promoted by the E2 enzyme Ubc13/Mms2 complex, the target proteins, E3 enzymes, and cellular mechanisms involving K63Ub chains are largely unresolved. In our previous analysis, we found that nucleic acids (RNA and ssDNA) have a pH-dependent effect on K63Ub chain formation in vitro. The mechanism of the pH-regulated promotion reaction is investigated by analyzing the conformational changes of Ubc13/Mms2, screening for nucleic acid binding sites, and nucleic acid binding analysis using high-speed AFM.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

新たなE2活性化メカニズムの発見と理解はユビキチン研究分野の発展につながる。核酸やpHによる酵素反応促進メカニズムの概念は、蛋白質科学全体に大きなインパクトを与えるだろう。細胞内でどれほどのpH環境の変化が存在するか、またそれに伴う活性制御機構のほとんどを我々は知らない。本研究で得られた高速AFMを含めた解析手法や結果は学術的にも独自性が高く、核酸に関連した生命機構全体においてブレークスルーの可能性を有しており、今後も創造性の高い発展が期待できる。