title: Chemomechanical coupling of human mitochondrial F1-ATPase motor.
abstract: The rotary motor enzyme F1-ATPase (F1) is a catalytic subcomplex of FoF1-ATP synthase that produces most of the ATP in respiring cells. Chemomechanical coupling has been studied extensively for bacterial F1 but very little for mitochondrial F1. Here we report ATP-driven rotation of human mitochondrial F1. A rotor-shaft γ-subunit in the stator α3β3 ring rotates 120° per ATP with three catalytic steps: ATP binding to one β-subunit at 0°, inorganic phosphate (Pi) release from another β-subunit at 65° and ATP hydrolysis on the third β-subunit at 90°. Rotation is often interrupted at 90° by persistent ADP binding and is stalled at 65° by a specific inhibitor azide. A mitochondrial endogenous inhibitor for FoF1-ATP synthase, IF1, blocks rotation at 90°. These features differ from those of bacterial F1, in which both ATP hydrolysis and Pi release occur at around 80°, demonstrating that chemomechanical coupling angles of the γ-subunit are tuned during evolution.
authors.affiliation: 1] Faculty of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, Japan. [2] ATP Synthesis Regulation Project, International Research Project (ICORP), Japan Science and Technology Corporation (JST), Miraikan, Koto-ku, Tokyo, Japan. [3] Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta, Yokohama, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: 1] ATP Synthesis Regulation Project, International Research Project (ICORP), Japan Science and Technology Corporation (JST), Miraikan, Koto-ku, Tokyo, Japan. [2] Department of Molecular Bioscience, Kyoto-Sangyo University, Kamigamomotoyama, Kyoto, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: ATP Synthesis Regulation Project, International Research Project (ICORP), Japan Science and Technology Corporation (JST), Miraikan, Koto-ku, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Wakabayashi
authors.affiliation: 1] ATP Synthesis Regulation Project, International Research Project (ICORP), Japan Science and Technology Corporation (JST), Miraikan, Koto-ku, Tokyo, Japan. [2] Department of Molecular Bioscience, Kyoto-Sangyo University, Kamigamomotoyama, Kyoto, Japan.
authors.forename: Ei-ichiro
authors.initials: E
authors.lastname: Saita
authors.affiliation: 1] Faculty of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, Japan. [2] ATP Synthesis Regulation Project, International Research Project (ICORP), Japan Science and Technology Corporation (JST), Miraikan, Koto-ku, Tokyo, Japan. [3] Department of Molecular Bioscience, Kyoto-Sangyo University, Kamigamomotoyama, Kyoto, Japan.
authors.forename: Masasuke
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001386:Azides / Q000494:pharmacology; D055162:Biocatalysis / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D012399:Rotation
chemical_list: D001386:Azides; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases