title: Rotation Mechanism of Molecular Motor V1-ATPase Studied by Multiscale Molecular Dynamics Simulation.
abstract: Enterococcus hirae V1-ATPase is a molecular motor composed of the A3B3hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A3B3ring undergo conformational changes, which lead to a 120° rotation of the central stalk. To understand how the conformational changes of three catalytic pairs induce the 120° rotation of the central stalk, we performed multiscale molecular dynamics (MD) simulations in which coarse-grained and all-atom MD simulations were combined using a fluctuation matching methodology. During the rotation, a catalytic AB pair spontaneously adopted an intermediate conformation, which was not included in the initial inputs of the simulations and was essentially close to the "bindable-like" structure observed in a recently solved crystal structure. Furthermore, the creation of a space between the bindable-like and tight pairs was required for the central stalk to rotate without steric hindrance. These cooperative rearrangements of the three catalytic pairs are crucial for the rotation of the central stalk.
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Isaka
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ekimoto
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kokabu
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamato
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Inage, Chiba, Japan; JST, PRESTO, Inage, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, Japan. Electronic address: ike@tsurumi.yokohama-cu.ac.jp.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012399:Rotation
chemical_list: D000251:Adenosine Triphosphatases