Structural analysis of cFLIP as an iron-binding protein and elucidation of a new physiological function

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Sakamaki Kazuhiro 京都大学, 生命科学研究科, 准教授 (20271017)
• Co-Investigator(Kenkyū-buntansha): 富井 健太郎 国立研究開発法人産業技術総合研究所, 情報・人間工学領域, 研究チーム長 (40357570)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞死 / 擬プロテアーゼ / 鉄結合タンパク質

Outline of Final Research Achievements

cFLIP is defined as a pseudo protease because it has lost its enzyme activity as a protease in the process of molecular evolution, but although the molecular evolution speed is fast, the certain amino acids in the pseudo protease-domain are conserved in vertebrates. We thought that there is some significance because they do not change during evolution. Our study demonstrated a new property of cFLIP as an iron-binding protein, suppressing the Fenton reaction with ferrous ions and hydrogen peroxide, and also inhibiting cell death induced by these factors.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、擬プロテアーゼと定義されたタンパク質がその後の進化によって新たな機能を獲得したことを立証した研究である。このことは、擬酵素と呼ばれながらも細胞で生成され続けるタンパク質についてその存在意義を再検証することを促す切っ掛けとなる。