Rotors of ATP synthases

A membrane-embedded rotor ring plays a central role in ion translocation during adenosine triphosphate (ATP) synthesis by proton- or sodium motive force-driven F1Fo-ATP synthases. These rotors consist of multiple copies of hairpin-like c-subunits, which form an hourglass-shaped cylinder with a central pore. The design of the c-ring rotor provides the ion (H+ or Na+) binding specificity of the enzyme. The stoichiometry of the c-ring equals the number of ion binding sites on the rotor-ring and this number determines the ion per ATP gearing ratio, an obviously important cell bioenergetic parameter. The stoichiometry of the rotor rings appears invariable for a selected species but variable in the range from 8 to 15 c-subunits within different species. In my talk I am going to focus on two central aspects of the rotor ring structure, ion binding and stoichiometry. Three different high-resolution structures of rotor rings from bacterial sources show possibilities of how Na+ or H+ can be coordinated during the ion translocation process through the membrane-embedded Fo complex. The structures suggest that the precise coordination chemistry keeps the ions in an ion locked conformation during the passage through the lipid/c-ring interface and an inhibitor bound structure shows the ion binding site in open conformation, which enables ion exchange. The data is directly supported by biochemical experiments as well as molecular dynamics studies. Site directed mutations at selected tightly packed regions of the complex within the c/c interface reveal that the stoichiometry can be influenced to form rotor rings of variable sizes and incorporated into operational ATP synthases, enabling us to engineer the gearing ratio of the enzyme. The results support the view that the quaternary structure of the rotor ring is determined by the primary structure of the c-subunit. The high grade of flexibility of the Fo rotor complexes offers a rationale for the variety of c-ring stoichiometries, which are manifested by different species in the course of the adaptation of their ATP synthases to their specific bioenergetic demands.