Structure of the F1-binding domain of the stator of bovine F1Fo-ATPase and how it binds an alpha-subunit.

The peripheral stalk of ATP synthase holds the alpha3beta3 catalytic subcomplex stationary against the torque of the rotating central stalk. In bovine mitochondria, the N-terminal domain of the oligomycin sensitivity conferral protein (OSCP-NT; residues 1-120) anchors one end of the peripheral stalk to the N-terminal tails of one or more alpha-subunits of the F1 subcomplex. Here we present the solution structure of OSCP-NT and an NMR titration study of its interaction with peptides representing N-terminal tails of F1 alpha-subunits. The structure comprises a bundle of six alpha-helices, and its interaction site contains adjoining hydrophobic surfaces of helices 1 and 5; residues in the region 1-8 of the alpha-subunit are essential for the interaction. The OSCP-NT is similar to the N-terminal domain of the delta-subunit from Escherichia coli ATP synthase (delta-NT), except that their surface charges differ (basic and acidic, respectively). As the charges of the adjacent crown regions in their alpha3beta3 complexes are similar, the OSCP-NT and delta-NT probably do not contact the crowns extensively. The N-terminal tails of alpha-subunit tails are probably alpha-helical, and so this interface, which is essential for the rotary mechanism of the enzyme, appears to consist of helix-helix interactions.