A research journey with ATP synthase

These reflections present a perspective of how I and my graduate students and postdoctoral fellows, over a span of many years, arrived at the concept that ATP is made by an unusual rotational catalysis of the ATP synthase. A recent sketch of the structure of this remarkable enzyme is given in Fig. 1. Such a depiction is the culmination of the efforts of many investigators.(1) The two portions of the enzyme are the membrane-imbedded F-0 and the attached F-1 that has three catalytic sites, principally on the large beta subunits. ATP is formed when protons pass through the F-0, driving the rotation of the ring-shaped cluster of c subunits and the attached epsilon and gamma subunits. Other subunits attached to outer portions of the F-0 and F-1 served as a stator. The internal rotary movement of the gamma subunit is coupled to sequential changes in the conformation of the catalytic sites. During ATP synthesis these conformational changes promote the binding of ADP and P-i, the formation of tightly bound ATP, and the release of ATP. Revealing the mechanism of the ATP synthase became a major. research goal in the latter part of my long career. This paper recalls how my career developed as related to the remarkable progress in biochemical knowledge. It presents the background and results of fruitful, as well as mistaken, approaches that were explored.