Isaka Yuta, Ekimoto Toru, Kokabu Yuichi, Yamato Ichiro, Murata Takeshi, Ikeguchi Mitsunori
Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, Japan.
Department of Biological Science and Technology, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.
Biophys J. 2017 Mar 14;112(5):911-920. doi: 10.1016/j.bpj.2017.01.029.
Enterococcus hirae V-ATPase is a molecular motor composed of the AB hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the AB ring 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.
平肠球菌V-ATP酶是一种由AB六聚体环和中心轴组成的分子马达。与ATP水解相关联，AB环中的三个催化AB对发生构象变化，这导致中心轴旋转120°。为了理解三个催化对的构象变化如何诱导中心轴旋转120°，我们进行了多尺度分子动力学（MD）模拟，其中粗粒度和全原子MD模拟使用波动匹配方法相结合。在旋转过程中，一个催化AB对自发地采用了一种中间构象，这种构象不包括在模拟的初始输入中，并且基本上接近最近解析的晶体结构中观察到的“可结合样”结构。此外，为了使中心轴无空间位阻地旋转，需要在可结合样对和紧密对之间形成一个空间。三个催化对的这些协同重排对于中心轴的旋转至关重要。
