Structure of the subunit c oligomer in the F1F0 ATP synthase: Model derived from solution structure of the monomer and cross-linking in the native enzyme

The structure of the subunit c oligomer of the H+-transporting ATP synthase of Escherichia coli has been modeled by molecular dynamics and energy mini mization calculations from the solution structure of monomeric subunit c an d 21 intersubunit distance constraints derived from cross-linking of subuni ts, Subunit c folds in a hairpin-like structure with two transmembrane heli ces, In the c(12) oligomer model, the subunits pack to form a compact hollo w cylinder with an outer diameter of 55-60 Angstrom and an inner space with a minimal diameter of 11-12 Angstrom. Phospholipids are presumed to pack i n the inner space in the native membrane. The transmembrane helices pack in two concentric rings with helix 1 inside and helix 2 outside, The calculat ions strongly favor this structure versus a model with helix 2 inside and h elix 1 outside. Asp-61, the H+-transporting residue, packs toward the cente r of the four transmembrane helices of two interacting subunits, From this position at the front face of one subunit, the Asp-61 carboxylate lies prox imal to side chains of Ala-24, Ile-28, and Ala-62, projecting from the back face of a second subunit. These interactions were predicted from previous mutational analyses. The packing supports the suggestion that a c-c dimer i s the functional unit. The positioning of the Asp-61 carboxyl in the center of the interacting transmembrane helices, rather than at the periphery of the cylinder, has important implications regarding possible mechanisms of H +-transport-driven rotation of the c oligomer during ATP synthesis.