The ATP synthase is found embedded in biological membranes, and exists as a complex of at least 24 proteins, depending upon the organism. Functionally, it has three components: Chemical, Mechanical, and Electrical. To start the motor a current of positively charged hydrogen ions (protons) must pass through the membrane-embedded proteins a and c. There are 12 copies of the c subunit, organized in a ring. The current causes the ring to rotate, like a water wheel, while the protons are delivered from one side of the membrane to the other. This rotary motion drives the "mechanical" proteins called gamma and epsilon. The gamma protein extends like a shaft into a central core formed by the "chemical" proteins called alpha and beta. The rotation of gamma causes each of the three beta proteins, in turn, to release the synthesized ATP. In fact, the ATP can form spontaneously in the friendly environment provided by the beta proteins, and the job of the gamma protein is to pry it loose. Once released, the ATP can be used elsewhere in the cell for a variety of tasks. This cycles repeats continuously----it is estimated that an active person will synthesize his or her body weight in ATP every day. Two other subunits not mentioned are called delta and b. They function as the "stator", keeping the alpha and beta proteins immobilized relative to the a protein. Gamma, epsilon, and c constitute the "rotor".

At SMU we are investigating the role of the epsilon and a proteins. One idea is that the epsilon helps the rotor work in a stepwise fashion, so that it rotates only one-third of a revolution at a time. The 3-dimensional structure of epsilon is now known. We are able to change the composition of epsilon by mutagenesis. In this way we can learn how different parts of epsilon are involved in rotary function. The a protein has been the most difficult of all to study. We have used mutagenesis to help develop a low-resolution structural model, and also to probe the proton pathway. It is clear now that the a protein helps initiate the proton current.