Activity and NMR structure of synthetic peptides of the bovine ATPase inhibitor protein,IF1

The protein IF₁ is a natural inhibitor of the mitochondrial F_oF₁-ATPase. Many investigators have been prompted to identify the shortest segment of IF₁, retaining its native activity, for use in biomedical applications. Here, the activity of the synthetic peptides IF₁-(42–58) and IF₁-(22–46) is correlated to their structure and conformational plasticity determined by CD and ¹H]-NMR spectroscopy. Among all the IF₁ segments tested, IF₁-(42–58) exerts the most potent, pH and temperature dependent activity on the F_oF₁ complex. The results suggest that, due to its flexible structure, it can fold in helical and/or β-spiral arrangements that favor the binding to the F_oF₁ complex, where the native IF₁ binds. IF₁-(22–46), instead, as it adopts a rigid -helical conformation, it inhibits ATP hydrolysis only in the soluble F₁ moiety.