The FOF1 ATP synthase: from atomistic three-dimensional structure to the rotary-chemical function

Abstract

Molecular motors are multi-subunit complexes that are indispensable for accomplishing various tasks of the living cells. One such molecular motor is the FOF1 ATP synthase that synthesizes ATP at the expense of the membrane proton gradient. Elucidating the molecular origin of the motor function is challenging despite significant advances in various experimental fields. Currently atomic simulations of whole motor complexes cannot reach to functionally relevant time scales that extend beyond the millisecond regime. Moreover, to reveal the underlying molecular origin of the function, one must model the coupled chemical and conformational events using physically and chemically meaningful multiscaling techniques. In this review, we discuss our approach to model the action of the F1 and FO molecular motors, where emphasis is laid on elucidating the molecular origin of the driving force that leads to directional rotation at the expense of ATP hydrolysis or proton gradients. We have used atomic structures of the motors and used hierarchical multiscaling techniques to generate low dimensional functional free energy surfaces of the complete mechano-chemical process. These free energy surfaces were studied further to calculate important characteristics of the motors, such as, rotational torque, temporal dynamics, occurrence of intermittent dwell states, etc. We also studied the result of mutating various parts of the motor domains and our observations correspond very well with the experimental findings. Overall, our studies have generated a cumulative understanding of the motor action, and especially highlight the crucial role of electrostatics in establishing the mechano-chemical coupling.

Toward Artificial Cells: Novel Advances in Energy Conversion and Cellular Motility

“…The production of ATP is, therefore, controlled by ATP synthase, and the main motive force of this process is the electrochemical gradient. Hence, the coupling of this proton‐motive force (PMF) and the ATP synthase on a membrane is sufficient for an ATP‐fueled artificial cell …”

“…Hence, the coupling of this protonmotive force (PMF) and the ATP synthase on a membrane is sufficient for an ATP-fueled artificial cell. [118]…”

Artificial Photosynthesis for Production of ATP, NAD(P)H, and Hydrogen Peroxide

“…Photoinduced charge separation in the photosynthetic reaction centers results in proton transfer from the stroma into the thylakoid lumen, which generates a proton motive force ( pmf ) across the thylakoid membrane . The pmf drives ATP synthesis by the function of the ATP synthase using ΔpH, which is the proton concentration gradient and the membrane potential (Δ Ψ ), which results from the charge difference across the thylakoid membrane . A pmf was generated by using a photosynthetic reaction center mimic triad (C‐P‐Q in Figure ) composed of a carotenoid polyene (C), a tetraarylporphyrin (P) and a naphthoquinone moiety fused to a norbornene unit with a carboxylic acid (Q), which was incorporated into the bilayer of a liposome .…”

Essential Role of the ε Subunit for Reversible Chemo-Mechanical Coupling in F1-ATPase

“…F o F 1 -ATP synthase (F o F 1 ) is one of the most ubiquitous enzymes, which mediates energy conversion among heterogeneous energy sources; in particular, by catalyzing ATP synthesis from ADP and inorganic phosphate (P i ) by using the proton motive force (pmf) across biomembranes (1)(2)(3)(4)(5). The prominent feature of F o F 1 is that mechanical rotation of the inner rotor complex mediates heterogeneous energy conversion with high efficiency and reversibility.…”