Abstract
The FO motor in FOF1 ATP synthase rotates its rotor driven by the proton motive force. While earlier studies elucidated basic mechanisms therein, recent advances in high-resolution cryo-electron microscopy enabled to investigate proton-transfer coupled FO rotary dynamics at structural details. Here, taking a hybrid Monte Carlo/molecular dynamics simulation method, we studied reversible dynamics of a yeast mitochondrial FO. We obtained the 36°-stepwise rotations of FO per one proton transfer in the ATP synthesis mode and the proton pumping in the ATP hydrolysis mode. In both modes, the most prominent path alternatively sampled states with two and three deprotonated glutamates in c-ring, by which the c-ring rotates one step. The free energy transduction efficiency in the model FO motor reached ~ 90% in optimal conditions. Moreover, mutations in key glutamate and a highly conserved arginine increased proton leakage and markedly decreased the coupling, in harmony with previous experiments. This study provides a simple framework of simulations for chemical-reaction coupled molecular dynamics calling for further studies in ATP synthase and others.
Highlights
The FO motor in FOF1 ATP synthase rotates its rotor driven by the proton motive force
We begin with simulations of rotary motions of FO motor driven by a proton-motive force, which corresponds to the ATP synthesis mode
Without external torque applied to the c10-ring, we performed proton-transfer coupled molecular dynamics (MD) simulations of the FO motor ac[10] with the pH difference between the inter membrane space (IMS) and matrix sides being 1 and the membrane potential ∆Ψ = 150 mV
Summary
The FO motor in FOF1 ATP synthase rotates its rotor driven by the proton motive force. The c-subunit has a key glutamate (cE59, throughout, the residue number is for yeast FOF1) nearly at the middle point in the membrane, which serves as the carrier of protons: A protonation in the cE59 allows c10-ring to hold a proton, whereas it is deprotonated upon a proton release. The recent cryo-electron microscopy (cryo-EM) studies[18,19] revealed the structure of FOF1 ATP synthase at atomic resolution and found two long tilted parallel α -helices in the a-subunit at the interface with c10-ring. It is experimentally confirmed that the mutation in this key arginine leads to proton leakage and decreases both the ATP synthesis and the proton pump activities for the thermophilic FOF121. It is impossible to observe the proton transfers through FO directly
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