Fig. 1: Bacterial ATP synthase architecture and ε-mediated inhibition.

a A schematic representation of bacterial F₁F_o ATP synthase in which subunits are labeled and color coded. Protons enter from the periplasm, driving the rotation of the c-ring. The central stalk (subunit γ, in blue) transfers this rotation to F₁, inducing conformational changes in its α and β subunits where catalysis occurs. b A schematic describing synthesis in the F₁-ATPase. A cross-section through the αβγ subunits shows that the catalytic subunits undergo conformational changes in response to γ subunit rotation. These changes facilitate the binding of ADP+Pi and synthesis of ATP. c A schematic describing proton driven rotation of the c-ring. Protons enter a half-channel from the periplasm and bind sequentially to a carboxylate on a c subunit. The ring rotates, and protons exit via another half-channel open to the cytoplasm. Subunit a contains an arginine residue between the half-channels that prevents short-circuiting of the motor. d Observed structural changes in E. coli ATP synthase show the ε subunit transitioning from an extended “up” (PDB: 6OQW) to a condensed “down” (PDB: 8DBW) conformation upon addition of ATP. In the extended conformation of ε, the εCTH2 inserts into the F₁-ATPase head, preventing closure of a β subunit and potentially inhibiting rotation and thus catalysis.