Strctural and Functional Dynamics on Proteins Related to Biometal Dynamics

2023 Fiscal Year Final Research Report

• Project Area: Integrated Biometal Science: Research to Explore Dynamics of Metals in Cellular System
• Project/Area Number: 19H05761
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: University of Hyogo
• Principal Investigator: SHIRO Yoshitsugu 兵庫県立大学, 理学研究科, 特任教授 (70183051)
• Co-Investigator(Kenkyū-buntansha): 澤井 仁美 長崎大学, 工学研究科, 准教授 (50584851)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 生体鉄 / 鉄動態 / トランスポーター / 鉄還元酵素 / 鉄センサータンパク質 / 鉄含有タンパク質 / フェリチン

Outline of Final Research Achievements

Iron is a bio-metal, which is essential in maintaining the lives of all living system. In this project, we have studies the dynamics of iron in cell (absorption, sensing, transport, storage, usage etc) on the basis of the dynamic structures and interaction of proteins related to the iron dynamics.
In human, the iron in diet is absorbed in duodenum, in which iron reductase (dcytb) and iron transporter (DMT1) play crucial roles. We studies the interaction of Dcytb with the iron by native MASS technique, and with DMT1 in cell to transport the ferrous iron resulted by the reduction of ferric iron by Dcytb by PLA assay.
We also studied the molecular mechanisms of heme inporter, heme sensor protein, and heme exporter in pothogenic bacteria, all of which play crucial roles in acquisition of iron. Especially, we focused on their dynamic structures in functionalization.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

従来の研究は、個別のタンパク質の静的な分子構造を基盤にしたものか、分子生物学あるいは細胞生物学を基盤にした細胞機能の記述が中心であったが、本研究の成功により「鉄の生体内動態に関する細胞機能を、関連するタンパク質群の分子構造・機能を基盤に記述する」ことが可能となった。これにより、鉄が関係する疾病、すなわち鉄の欠乏や過剰が引き起こす重篤な疾病の根本原因の究明や治療に関して、得られた研究成果が直接関与することを目指した。さらに、この研究のために新しく開発した測定解析法は、他の研究分野にも広く応用可能である。