A perspective of the binding change mechanism for ATP synthesis.

An overview of research in the field of bioenergetics that led to the development of the binding change mechanism for ATP synthesis is presented, with emphasis on research from the author's laboratory. The text follows closely the Rose Award Lecture given at the 1989 meeting of the American Society for Biochemistry and Molecular Biology. Remarkable advances have revealed that the ubiquitous membrane-bound ATP synthase has unusual composition and properties. The enzyme complex has 1, 2, 3, or 9-12 copies of eight or more protein subunits. The catalytic sites are located on three copies of an approximately 55-kDa subunit. It has the strongest positive catalytic cooperativity known for any enzyme. Examples are given of selected experimental results that have provided insights into its mechanism. These include demonstration of the characteristics, location, and function of catalytic and noncatalytic adenine nucleotide binding sites and the incisive information provided by measurement of phosphate oxygen exchanges and distribution of 18(O) in ATP or Pi formed by catalysis. Research from various laboratories gives support to the binding change mechanism in which energy from proton translocation serves principally to promote release of tightly bound ATP, with sequential participation of three catalytic sites. Some speculative suggestions about a rotational catalysis and about the different forms assumed by the ATPase are included.