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

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