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

Abstract

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 αDPDP 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.

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Figure 1: The dimeric bovine F1-ATPase–IF1 complex.
Figure 2: Regions of the electron density map of the F1−IF1 complex.
Figure 3: Stereo view of the contacts between F1-ATPase and IF1.
Figure 4: Conformational changes in the F1−IF1 complex relative to the reference state of F1-ATPase.
Figure 5: The catalytic interface between subunits αDP and βDP in the reference state structure of F1-ATPase and in the F1−IF1 complex.
Figure 6: The inhibition of the ATP hydrolytic activity of ATP synthase by IF1.

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Acknowledgements

We thank the staff of beamline ID14 at European Synchrotron Radiation Facility (ESRF), Grenoble, for help with data collection. E.C. was supported during part of this work by a European Molecular Biology Organization Fellowship and by a TMR Marie Curie Research Training Grant from the European Community.

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Correspondence to Andrew G W Leslie or John E Walker.

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Cabezón, E., Montgomery, M., Leslie, A. et al. The structure of bovine F1-ATPase in complex with its regulatory protein IF1. Nat Struct Mol Biol 10, 744–750 (2003). https://doi.org/10.1038/nsb966

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