The ATPase asymmetry: Novel computational insight into coupling diverse FO motors with tripartite F1.

Abstract

ATP synthase, a crucial enzyme for cellular bioenergetics, operates via the coordinated coupling of an F_O motor, which presents variable symmetry, and a tripartite F₁ motor. Despite extensive research, the understanding of their coupling dynamics, especially with non-10-fold symmetrical F_O motors, remains incomplete. This study investigates the coupling patterns between eightfold and ninefold F_O motors and the constant threefold F₁ motor using coarse-grained molecular dynamics simulations. We unveil that in the case of a ninefold F_O motor, a 3-3-3 motion is most likely to occur, whereas a 3-3-2 motion predominates with an eightfold F_O motor. Furthermore, our findings propose a revised model for the coupling method, elucidating that the pathways' energy usage is primarily influenced by F₁ rotation and conformational changes hindered by the b-subunits. Our results present a crucial step toward comprehending the energy landscape and mechanisms governing ATP synthase operation.