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 A3B3 hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A3B3 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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Isaka Y,Ekimoto T,Kokabu Y,Yamato I,Murata T,Ikeguchi M

doi

10.1016/j.bpj.2017.01.029

subject

Has Abstract

pub_date

2017-03-14 00:00:00

pages

911-920

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(17)30154-6

journal_volume

112

pub_type

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