Brønsted slopes based on single-molecule imaging data help to unveil the chemically coupled rotation in F₁-ATPase

F₁-ATPase, the rotary motor that powers most of the processes in living cells, has challenged scientists, experimentalists, and theoreticians alike to gain deeper understanding of its action. The work on F₁ for more than two decades encompasses elucidation of the complex 3D structure (1) and the analysis of the thermodynamics and kinetics of the chemical steps (2) that led to the revelation of its rotary–chemical action (3). These advances were enhanced by direct observation of the F₁ central stalk (γ) rotation (4) that is tightly coupled to the chemical steps of the ATP binding, hydrolysis, and product release, occurring in the three catalytic subunits of the crown (α/β). The γ rotation was observed to occur in substeps of 80°/40° that were embedded within the waiting dwells, namely, the “ATP binding dwell” before the 80° substep and the “catalytic dwell” before the 40° substep (5) (Fig. 1). Since the initial progress made almost two decades ago, the study of various aspects of F₁ continues to occupy a central position, as ongoing efforts offer more detailed insights into the structure, function, and dynamics of the system (6, 7).

↵¹To whom correspondence should be addressed. Email: warshel{at}usc.edu.