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The distortion-push mechanism for the γ subunit rotation in F1-ATPase
Masahiro Motohashi1,2, Mao Oide2,3, Chigusa Kobayashi4
1Department of Physics, Faculty of Science and Engineering, Chuo University, Tokyo 112-8551, Japan.
Summary
The F1-ATPase rotor
Area of Science:
- Biochemistry and Molecular Biology
- Structural Biology
- Computational Biophysics
Background:
- F1-ATPase, a molecular motor, utilizes a rotating gamma (γ) subunit within a stator ring of alpha (α)3β3 subunits.
- Understanding the γ subunit rotation mechanism is crucial for elucidating ATP hydrolysis and synthesis.
- Recent cryo-electron microscopy (cryo-EM) structures of thermophilic F1-ATPase (TF1) offer new insights.
Purpose of the Study:
- To investigate the relationship between γ subunit rotation, stator α3β3 subunit conformational changes, and nucleotide binding/release.
- To elucidate the mechanism of the 80° substep rotation of the γ subunit in F1-ATPase.
Main Methods:
- Targeted molecular dynamics (MD) simulations with external forces applied to the α3β3 subunits.
- Mean-force string method simulations to optimize the transition pathway.
- Umbrella sampling to calculate the potential of mean forces along the minimum free energy pathway.
Main Results:
- MD simulations revealed an 80° substep rotation of the γ subunit, divided into initial rotation, resting, and final rotation phases.
- The initial rotation is driven by stator α3β3 subunit distortion.
- The final rotation is primarily induced by direct interactions between the β and γ subunits.
Conclusions:
- A 'distortion-push' mechanism is proposed for the 80° γ subunit substep rotation in F1-ATPase.
- This mechanism integrates stator distortion and direct subunit interactions.
- The findings align with experimental residue-level analyses and high-resolution structural data (X-ray crystallography and cryo-EM).
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