F-ATP synthases are the most prominent ATP source across the living world. These enzymes couple the structural changes required for catalyzing the conversion of ADP and Pi into ATP to the transmembrane flow of protons or sodium ions down their electrochemical gradients. The key, coupling element in these molecular machines is the membrane-embedded Fo rotor, or c-ring. The recent emergence of high-resolution structural data and the close interplay of experimental methods with advanced, quantitative molecular simulations are providing novel and important insights into the mechanisms of these essential proteins. We present an overall summary of our recent progress in this area, particularly pertaining to the mechanism by which ion exchange across the lipid membrane is coupled to the rotation of the c-ring, as well as to the structural basis for the distinct ion-binding selectivity observed for different species. We believe these principles may well apply more generally in the context of ion-coupled membrane transport.View Large Image | View Hi-Res Image | Download PowerPoint SlideMeier […] Faraldo-Gomez (2009). J. Mol. Biol. 391:498-507.Pogoryelov […] Faraldo-Gomez, Meier. (2009). Nat. Struct. Mol. Biol. (in press).Krah […] Meier, Faraldo-Gomez (2009). J. Mol. Biol. (under review).