The elaborately designed domain motion of the multidomain protein CCS and its physical origin

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22629
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Shimizu Masahiro 京都大学, 複合原子力科学研究所, 研究員 (00879869)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 分子動力学シミュレーション / 金属タンパク質 / 銅タンパク質 / 小角散乱法

Outline of Final Research Achievements

Copper chaperone for superoxide dismutase (CCS) is a protein consisting of multiple structural domains, and responsible for intracellular copper ion transport to an enzyme. The relationship between function and molecular motion of CCS was studied by small-angle X-ray scattering and computational simulations. Our results suggested the significance of cooperation of all structural domain including a domain which does not bind copper ion for copper binding or holding of CCS. To obtain the result above, we also established a modeling method for visualizing possible behavior of a biomolecule which combines molecular dynamics simulation and small-angle scattering data. Our idea is that when a long-time molecular dynamics simulation of a biomolecules matches a small-angle scattering profile of the molecule, the simulation trajectory is regarded as a possible structural pool of that. Feasibility of the idea was confirmed for some proteins.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究で提案した溶液散乱測定と理論計算による分子運動解析のアイデアは、今まで困難であった「X線結晶構造等の原子解像度データと、低解像度ながらも分子運動情報を含む小角散乱データを統合した生体分子ダイナミクス理解」への新規な道筋を与えている。加えて、この解析は他の実験データにも応用可能であり、様々な生体高分子実験データを統合し生体分子への理解を深めるための普遍的技術たりうることから、広く関連学術分野への波及効果が期待される。