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ATP synthase couples a membrane-embedded rotary motor to a soluble catalytic head. Its membrane sector contains a rotating ring of c subunits and a stationary a subunit providing offset proton-access pathways. Its catalytic sector contains an ${\alpha }_3{\beta }_3$ head with catalytic sites primarily on the $\beta$ subunits, a central rotating shaft, and a peripheral stator that prevents the head simply co-rotating.

A proton-motive force, combining a membrane potential and a proton chemical potential difference, drives directional proton passage and ring rotation. Rotation of the central shaft changes the conformations and binding affinities of successive catalytic sites, allowing ADP and inorganic phosphate to bind, form ATP, and release it in a coordinated cycle. The ATP synthase rotary mechanism therefore couples ion transport, torque, and chemical work rather than requiring a proton to react directly at every catalytic site.

The motor is reversible: sufficiently favorable ATP hydrolysis can drive proton pumping against its electrochemical potential gradient. In mitochondria, the respiratory chain establishes the gradient used for oxidative ATP production; analogous coupling operates in bacterial membranes and in chloroplast photophosphorylation. The number of protons per revolution depends on the c-ring stoichiometry, whereas a full catalytic rotation normally produces three ATP molecules. It is therefore inappropriate to assign one universal integer proton-to-ATP ratio to all organisms. Transport and leakage can increase the whole-cell energetic cost beyond the motor's ideal ratio.

The central prediction of the ATP synthase ATP synthase rotary mechanism is relative motion of the central shaft and catalytic head, not simply a change in bulk ATP concentration. In the foundational single-molecule experiment, a visible marker coupled to the central gamma shaft reported its angular position relative to the immobilized catalytic head. Sustained directional rotations during ATP hydrolysis demonstrated rotary motion directly. The catalytic head contains three beta sites within an alpha-three beta-three assembly; their changing nucleotide affinities motivate the binding-change mechanism. ^[ref]

An angular trajectory gives more information than an average rotational speed. At low ATP, pauses before roughly 120-degree advances become longer as ATP falls, supporting an ATP-binding-limited wait. Reducing marker drag and improving temporal resolution reveals substeps and ATP-independent catalytic dwells. The early high-speed study resolved approximately 90-degree and 30-degree substeps, with more than one slow event during the catalytic dwell. Numerical angles vary with preparation and operational definition, so these observations should not be imposed as exact universal geometric increments.^[ref]

The dwell-time model in b tests serial chemical kinetics; the angle histogram tests preferred positions. Comparing probe loads checks whether viscous drag limits the observed speed. Measuring torque and angular displacement estimates mechanical work, while a separate hydrolysis readout tests chemical coupling. With one ATP per 120-degree step, the chemical budget per revolution is three ATP, but rotation alone does not count every chemical event or establish unity efficiency.

A probe can perturb the very process it reports, and inhibited pauses or unresolved reversals can bias averages. Isolated F1 observed during hydrolysis also does not demonstrate proton-driven ATP synthesis by intact membrane F0F1. Testing reverse synthesis requires evidence for chemical gene expression under the corresponding driving conditions; a rotation movie by itself is insufficient. These distinctions connect the single-molecule motion to the free-energy balance without overinterpreting it.

A major source of ATP is chemiosmosis: an electron transport chain uses downhill electron transfer to establish a proton-motive force, and ATP synthase converts that electrochemical gradient into ATP formation. In aerobic oxidative phosphorylation, reduced carriers supply electrons, ultimately reducing oxygen to water; selected respiratory complexes couple the favorable oxidation-reduction reaction to uphill proton translocation. In a mitochondrion, this takes place across the inner membrane, creating a relatively positive, acidic exterior side and a relatively negative, alkaline matrix. Bacteria use their cell membrane. In photosynthetic systems, light-driven electron transfer can supply the gradient instead. Substrate-level phosphorylation is another ATP-producing route, so the description is not universal to every organism and condition.

The membrane $F_O$ region of ATP synthase contains a rotating ring of c-subunits next to subunit a. Two offset aqueous half-channels expose the ring's proton-binding sites to opposite membrane sides. Proton binding and release bias ring rotation down the electrochemical gradient. The central shaft transfers torque to the $F_1$ catalytic head, while a peripheral stator prevents the head from simply co-rotating. This is the ATP synthase rotary mechanism, rather than unrestricted proton leakage through a pore.

The three catalytic beta subunits cycle through different binding states as the shaft turns: ADP and inorganic phosphate bind, bound ATP is favored, then ATP is released. The binding-change mechanism uses mechanical work to alter binding affinities and product release as well as the chemical step. A full coupled revolution produces three ATP molecules; a ring with $n_c$ c-subunits transfers approximately $n_c$ protons per revolution in the tightly coupled model, or $n_c/3$ per ATP.^[ref][ref]

The overall cycle must have a favorable Gibbs free energy change. If the proton-motive force becomes too small, synthesis stops; under suitable conditions the same molecular motor can reverse, using ATP hydrolysis to pump protons uphill. A catalyst changes kinetics, not the thermodynamic condition for synthesis.