Subunit Arrangement in Bovine Mitochondrial H⁺-ATPASE

Abstract

The ATP-synthase or H⁺-ATPase of mitochondria is a multisubunit enzyme that couples the energy of a transmembrane proton gradient to the reversible synthesis of ATP (Pedersen, 1983; Hatefi, 1985). The enzyme is comprised of two sectors: the extrinsic sector F₁ carries the catalytic centers and the membrane-intercalated sector F₀ constitutes the proton conduction pathway through the membrane. These two sectors are believed to be connected by another morphologically distinct entity known as the stalk (Soper et al., 1979), The F₁-ATPase from all known sources contains five nonidentical subunits termed α, β, γ, δ and ε in a stoichiometry of 3:3:1:1:1 respectively (Wakabayashi et al., 1977). The composition of F₀ is species-dependent. The E. coli F₀ (the simplest so far defined) contains three subunits designated a, b and c (Senior and Wise, 1983). Mitohondrial F₀ is considerably more complex and contains at least thirteen subunits. Two of these, namely oligomycin-sensitivity-conferring protein (OSCP) and coupling factor 6 (F₆), are considered to constitute the stalk segment that separates F₁ from the membrane segment (Hatefi, 1985). The organization of the stalk subunits, and how they interact with other F₀ subunits or subunits of F₁ is not clear. However, to understand the functional roles of the polypeptides which comprise a multisubunit complex, a knowledge of their subunit arrangement is essential. A plausible arrangement of subunits in F₁ has been deduced from cross-linking experiments and from X-Ray diffraction studies, but little is known about the organization of subunits belonging to the F₀ region.