pH dependent conformational changes modulate functional activity of the mitochondrial ATPase inhibitor protein.

A 12kDa, heat stable protein (IF1) inhibiting hydrolytic activity of submitochondrial particles was purified to electrophoretic homogeneity from buffalo heart mitochondria. Specific activity of the purified fraction was > 5000 units/mg. Maximal inhibition was observed at pH 6.0 and was Mg++ and ATP dependent. Circular dichroism studies showed that the inhibitor peptide undergoes a dramatic, reversible conformational change in response to pH which correlates well with its ability to inhibit ATP hydrolysis catalyzed by inhibitor depleted submitochondrial particles. It is shown for the first time that IF1 with a predominantly beta-sheet component is more efficient at suppressing ATPase activity.