The structure of bovine F1-ATPase in complex with its regulatory protein IF1

In mitochondria, the hydrolytic activity of ATP synthase is prevented by an inhibitor protein, IF1. The active bovine protein (84 amino acids) is an α-helical dimer with monomers associated via an antiparallel α-helical coiled coil composed of residues 49–81. The N-terminal inhibitory sequences in the active dimer bind to two F1-ATPases in the presence of ATP. In the crystal structure of the F1−IF1 complex at 2.8 Å resolution, residues 1–37 of IF1 bind in the αDP-βDP interface of F1-ATPase, and also contact the central γ subunit. The inhibitor opens the catalytic interface between the αDP and βDP subunits relative to previous structures. The presence of ATP in the catalytic site of the βDP subunit implies that the inhibited state represents a pre-hydrolysis step on the catalytic pathway of the enzyme.