Protein structure analysis in human cell using advanced in-cell NMR techniques

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Yokohama National University
• Principal Investigator: KOJIMA Chojiro 横浜国立大学, 大学院工学研究院, 教授 (50333563)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: NMR / 蛋白質 / 立体構造解析

Outline of Final Research Achievements

The molecular functions of proteins are regulated by their three-dimensional structures. NMR is the only technique capable of analyzing the structure of proteins inside living cells while maintaining their cellular environment. However, structural analysis of proteins within living cells has been challenging, and there was no report of protein structure determination in living human cells. In this study, we developed a technique for analyzing the three-dimensional structures of proteins in human living cells using an innovative technology that achieved ultra-high sensitivity, known as in vivo/in cell NMR. Furthermore, we expanded the ultra-high sensitivity in vivo/in cell NMR method to enable real-time measurements of structural changes in proteins and phosphorus metabolism within human living cells.

Free Research Field

構造生命科学

Academic Significance and Societal Importance of the Research Achievements

蛋白質の機能は立体構造によって制御されています。NMRは細胞内の蛋白質を細胞が生きている状態のまま構造解析できる唯一の手法ですが、生細胞内での蛋白質の立体構造解析技術には再現性や検出感度に問題がありました。本研究では独自技術で超高感度化に成功したNMR技術を用い、ヒト生細胞内蛋白質の立体構造決定に成功しました。この研究の成果は、生体内での蛋白質の構造解析において画期的な進展であり、蛋白質研究や医薬品開発における重要な貢献が期待されます。