Analysis of intermediate states in the reaction process of iron-sulfur cluster biosynthesis machineries

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03204
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Saitama University
• Principal Investigator: Takahashi Yasuhiro 埼玉大学, 理工学研究科, 名誉教授 (10154874)
• Co-Investigator(Kenkyū-buntansha): 藤城 貴史 埼玉大学, 理工学研究科, 准教授 (20740450) ; 和田 啓 宮崎大学, 医学部, 教授 (80379304)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 鉄硫黄クラスター / 鉄硫黄タンパク質 / 生合成

Outline of Final Research Achievements

In this study, we analyzed the biosynthetic systems of iron-sulfur (Fe-S) clusters and clarified the following key points. (1) We clarified the reaction and inhibition mechanisms of cysteine desulfurase that supplies sulfur to the Fe-S clusters. (2) We captured the structure of IscU, a core component of the ISC machinery, in a state that retains the labile biosynthetic intermediate of the Fe-S cluster, and also clarified the significance of the conformational change of IscU induced by HscA-HscB. (3) We identified the SufB*2C2 type, which is distributed in anaerobic archaea and bacteria, as a prototype of the SUF machinery, and clarified the path and factors of the evolutionary changes of the biosynthetic systems.

Free Research Field

生化学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、Fe-Sクラスター生合成システムの作動機構と多様性について、鍵となるいくつかのポイントを世界に先駆けて明らかにすることができた。独自に研究の方向性を見定めて、オリジナルのin vivo実験系とin vitroの生化学的ならびに構造解析を有機的に関連させつつ発展させた成果である。これらはFe-Sクラスター生合成の本質に迫る重要な知見であり、学術的な意義は極めて大きい。