The structure of bovine IF1, the regulatory subunit of mitochondrial F-ATPase

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Abstract
In mitochondria, the hydrolytic activity of ATP synthase is regulated by an inhibitor protein, IF1. Its binding to ATP synthase depends on pH, and below neutrality, IF1 is dimeric and forms a stable complex with the enzyme. At higher pH values, IF1 forms tetramers and is inactive. In the 2.2 Å structure of the bovine IF1 described here, the four monomers in the asymmetric unit are arranged as a dimer of dimers. Monomers form dimers via an antiparallel α‐helical coiled coil in the C‐terminal region. Dimers are associated into oligomers and form long fibres in the crystal lattice, via coiled‐coil interactions in the N‐terminal and inhibitory regions (residues 14–47). Therefore, tetramer formation masks the inhibitory region, preventing IF1 binding to ATP synthase.