Structure and Conformations of the Bovine ATP Synthase by Single Particle Electron Cryomicroscopy

Adenosine triphosphate (ATP), the energy currency of cellular biology, is synthesized by the mitochondrial ATP synthase in most eukaryotes. Proton translocation in the membrane-bound FO region leads to ATP synthesis in the catalytic F1 region through rotation of a central rotor. The generation of rotation is proposed to occur through a Brownian ratchet mechanism requiring two offset half-channels in the FO region. Here, using single-particle electron cryomicroscopy (cryo-EM), seven distinct conformations within three rotational states of the ATP synthase are presented at sub-nanometre resolution. An average of the FO region of all seven maps provided a detailed view of the proton-translocating a subunit, allowing an atomic model to be built using evolutionary co-variance. The arrangement of subunits in the membrane region suggests two half-channels for proton translocation. These channels, along with an observed oscillation of the c8-ring in the FO region between substates in each rotational state, supports the Brownian ratchet mechanism for the generation of rotor rotation and ATP synthesis.M.Sc