Abstract

The F1F0 ATP synthase complex of Escherichia coli functions reversibly in coupling proton translocation to ATP synthesis or hydrolysis. The structural organization and subunit composition corresponds to that seen in many other bacteria, i.e. a membrane extrinsic F1 sector with five subunits in an alpha 3 beta 3 gamma delta epsilon stoichiometry, and a membrane-traversing F0 sector with three subunits in an a1b2c12 stoichiometry. The structure of much of the F1 sector is known from a X-ray diffraction model. During function, The gamma subunit is known to rotate within a hexameric ring of alternating alpha and beta subunits to promote sequential substrate binding and product release from catalytic sites on the three beta subunits. Proton transport through F0 must be coupled to this rotation. Subunit c folds in the membrane as a hairpin to two alpha helices to generate the proton-binding site in F0. Its structure was determined by NMR, and the structure of the c oligomer was deduced by cross-linking experiments and molecular mechanics calculations. The implications of the oligomeric structure of subunit c will be considered and related to the H+/ATP pumping ratio, P/O ratios and the cation-binding site in other types of F0. The possible limits of the structure in changing the ion-binding specificity, stoichiometry and routes of proton entrance/exit to the binding site will be considered.