P-type pump ; Molecular basis of energy coupling and carcinogenesis caused by defects

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04346
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Asahikawa Medical College
• Principal Investigator: Suzuki Hiroshi 旭川医科大学, 医学部, 教授 (50183421)
• Co-Investigator(Kenkyū-buntansha): 山崎 和生 旭川医科大学, 医学部, 講師 (60241428) ; 安田 哲 旭川医科大学, 医学部, 助教 (80749896) ; 大保 貴嗣 旭川医科大学, 医学部, 准教授 (90207267)
• Research Collaborator: MASAIKE Tomoko ; MINOWA Osamu ; DANKO Stefania
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: Ca-pump / active transport / flippase / energy coupling / P-type ATPase

Outline of Final Research Achievements

Gating mechanism of sarco(endo)plasmic reticulum Ca-pump SERCA1a and involvement of lipid on membrane in the pump function were studied, thereby understanding of energy coupling mechanism in the active Ca2+ transport were further deepened. By the use of the Ca2+-pump, the methods for a single molecule dynamics were developed, and the structural changes of the pump were analyzed for understanding the structural mechanism. For the flippase, another P-type ATPase, studies were performed to identify its specific substrates, and reveal the mechanism. Fur types of mutations of endoplasmic Ca2+-pump SERCA2b that develop squamous cell carcinoma in mouse model were identified, and the pathological consequences and defects in the pump protein were revealed.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

Caポンプの作動機序、即ち如何に構造が大きく変化し、如何なる構造領域が如何なる役割を果たし、ポンプ機能を成立させるかを「分子解剖学」により次々に露わにできた。またポンプ異常と病態脂質二重層形成機序の理解を深めると共に、さらに膜蛋白全般について作動機序解明の研究基盤を実例を持って形成した。
2017年度には、当該分野のほとんどすべての著名な、また若手の研究者を集め、滋賀県大津にて国際会議（P-type international meeting）を主催し、深い議論と交流の場を設け、国際交流と共に当該分野の今後の発展のため、また日本がその中心となって今後も深く貢献するための基盤さらに強くした。