On the Functional Differentiation of F- and V-Type Rotary Atpases Atomic Mechanism of a Hybrid F/V Membrane Rotor
Rotary ATPases/ATP synthases have a common architecture and overall mechanism, whereby the activity of the soluble catalytic domain is coupled to the rotation of a membrane-embedded sub-complex, or c-ring, which in turn is coupled to the translocation of H+ or Na+ across the membrane. Physiologically, however, V-ATPases function only as ion pumps, while F-type enzymes function as ATP synthases. It has been proposed that this differentiation stems from the greater spacing between consecutive ion-binding sites along the circumference of V-type c-rings, relative to the F class, resulting from the different topology of the constituent c-subunits. Here, we use molecular simulation methods and bioinformatic tools to assess the atomic mechanism of the Na+-coupled ATP synthase from Acetobacterium woodii, whose unusual c-ring features one V-type c-subunit inserted along nine of the F-type, and therefore lacks one ion-binding site. Our results demonstrate that rotation of the A. woodii c-ring in either direction is not fundamentally hampered by the inserted V-type c-subunit, and explain in atomic detail why this enzyme can be driven by a transmembrane Na+-gradient and thus function as an ATP synthase. In sum, we conclude that the physiological differentiation between V- and F-type enzymes is likely to arise primarily from the availability of suitable substrates and ionic gradients in the specific environment of these enzymes, rather than from a precise structural feature.