High-resolution structural analysis of mitochondrial supercomplex and ATP synthase involved in ATP synthesis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03646
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: University of Hyogo
• Principal Investigator: Shinzawa-Itoh Kyoko (新澤恭子) 兵庫県立大学, 生命理学研究科, 特任准教授 (70206316)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 呼吸鎖超複合体 / ATP合成酵素 / ミトコンドリア / 呼吸鎖電子伝達系 / 複合体Ⅳ

Outline of Final Research Achievements

Mitochondrial respiratory complex I, III and IV organized into super complex convert energy from a series of electron transfer into a proton electrochemical gradient, harvested by complex V for synthesis of ATP. The structure and functions of the super complex and each respiratory complex, purified from bovine heart to retain their original structure and functions, were compared. In all crystals reported to date, bovine complex IV exists as a dimer. Based on the structural and functional comparison of the monomer and dimer, we propose that the monomer is the activated form. Two cardiolipins are located at the interface region in the super complex. The visible resonance Raman spectra of purified reactive super complex and mixture of its individual components enabled us to discuss the detailed active site structures, but no detectable differences were observed. This indicates that the formation of a super complex did not markedly change the structure or electronic state of heme.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

2量体結晶構造が詳細に解明されてきた複合体Ⅳは、膜内及び超複合体内では単量体で存在し、単量体が活性型である事を示した。単量体結晶のX線結晶構造はカルジオリピンが複合体Ⅳの2量体形成ではなく複合体Ⅰ、Ⅲとの相互作用に関わることを示した。超複合体と各複合体混合溶液の振動分光学解析は会合が活性中心の大きな構造変化を伴わない事を示した。また、高い呼吸活性を示すが、比較的不飽和度が低く短鎖の脂質を含む流動性のある膜内で、密度を及び電子伝達体の割合を高くすることにより超複合体形成を伴わないで効率の良いATP合成を可能にしているショウジョウバエの適応は、ミトコンドリア内でのATP産生調節の多様性を示した。