Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases

In Saccharomyces cerevisiae, at least three proteins (IF1, STF1, and STF2) appear to be involved in the regulation of ATP synthase. Both IF1 and STF1 inhibit F-1, whereas the proposed function for STF2 is to facilitate the binding of IF1 and STF1 to F-1. The oligomerization properties of yeast IF1 and STF1 have been investigated by sedimentation equilibrium analytical ultracentrifugation and by covalent cross-linking. Both techniques confirm that IF1 and STF1 oligomerize in opposite directions in relation to pH, suggesting that both proteins might regulate yeast F1F0-ATPase under different conditions. Their effects on bovine F-ATPases are also described. Whereas bovine IF1 inhibits yeast F-1-ATPase even better than yeast IF1 or STF1, the capability of yeast IF1 to inhibit the bovine enzyme is very low and decreases with time. Such an effect is also observed in the study of the homologous inhibition of yeast F-1-ATPase. Yeast inhibitors are not as effective as their bovine counterpart, and the complex seems to dissociate gradually.