ATP Synthesis by Oxidative Phosphorylation

The F1F0-ATP synthase (EC 3.6.1.34) is a remarkable enzyme that functions as a rotary motor. It is found in the inner membranes of Escherichia coli and is responsible for the synthesis of ATP in response to an electrochemical proton gradient. Under some conditions, the enzyme functions reversibly and uses the energy of ATP hydrolysis to generate the gradient. The ATP synthase is composed of eight different polypeptide subunits in a stoichiometry of α3β3γδεab2c10. Traditionally they were divided into two physically separable units: an F1 that catalyzes ATP hydrolysis (α3β3γδε) and a membrane-bound F0 sector that transports protons (ab2c10). In terms of rotary function, the subunits can be divided into rotor subunits (γεc10) and stator subunits (α3β3δab2). The stator subunits include six nucleotide binding sites, three catalytic and three noncatalytic, formed primarily by the β and α subunits, respectively. The stator also includes a peripheral stalk composed of δ and b subunits, and part of the proton channel in subunit a. Among the rotor subunits, the c subunits form a ring in the membrane, and interact with subunit a to form the proton channel. Subunits γ and ε bind to the c-ring subunits, and also communicate with the catalytic sites through interactions with α and β subunits. The eight subunits are expressed from a single operon, and posttranscriptional processing and translational regulation ensure that the polypeptides are made at the proper stoichiometry. Recent studies, including those of other species, have elucidated many structural and rotary properties of this enzyme.