Understanding a mechanism regulating intracellular dynamics of metal ions

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04768
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Keio University
• Principal Investigator: Furukawa Yoshiaki 慶應義塾大学, 理工学部(矢上), 准教授 (40415287)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 銅タンパク質

Outline of Final Research Achievements

To understand intracellular dynamics of metal ions (copper ions, in particular), I have focused upon Cu/Zn-superoxide dismutase (SOD1), which is one of the most important copper proteins, as well as the copper chaperone protein CCS that supplies copper ions to SOD1. This study has suggested a new mechanistic action of CCS on SOD1 upon the copper supply and also newly identified a protein interacting with CCS. Furthermore, the breakdown of a copper supplying step to SOD1 was evaluated as a possible pathological change occurring in a neurodegenerative disease, amyotrophic lateral sclerosis (ALS). Misfolded SOD1 that is unable to bind copper ions has been proposed as a pathogenic species causing ALS.

Free Research Field

生物無機化学

Academic Significance and Societal Importance of the Research Achievements

生体における金属イオンの重要性・危険性は広く認識されている一方で、金属イオンの基本的な細胞内動態・挙動については多くのことが明らかとなっていない。本研究で扱う銅タンパク質SOD1は、活性酸素であるスーパーオキシドを不均化し、酸化ストレスの軽減を担う重要なタンパク質である。よって、SOD1を中心に、細胞内銅イオンの質的・量的恒常性を維持するメカニズムに迫る本研究は、基礎科学のみならず医学的にも意義のある研究で、神経変性疾患や各種の加齢性疾患などに対する分子標的治療薬の開発に貢献できると期待される。