Nature Structural & Molecular Biology pp 135 - 141 and 142 - 148

How cells convert many forms of energy into ATP, the universal energy currency of life, is a fundamental question in biology. Two papers in the February issue of Nature Structural & Molecular Biology now make important contributions toward answering this question. The first study provides evidence linking a specific direction of rotation of an ATP synthesizing machine to the generation of ATP. The second study links the discrete steps of rotation of this machinery with the chemical events occurring during ATP hydrolysis. These results provide insights into how a cell interconverts chemical energy and mechanical energy.

F0F1-ATP synthase is a protein complex that spans cellular membranes. It converts the energy stored in the form of pH differential across the membrane to that stored as a chemical bond in ATP. Under certain conditions, however, it can also reverse the reaction to consume ATP. Although part of this ATP synthase has been shown to be a nanomotor and can rotate, until now there has been no evidence directly linking the direction of rotation of the synthase with the pH differential or with the generation of ATP. Using single-molecule biophysical techniques, B�rsch and colleagues observed that a pH differential across a membrane drives the rotation of the ATP synthase in one specific direction during ATP synthesis. They also show that the rotation of the synthase during ATP synthesis occurs in three discrete 120-degree steps.

In a separate study, Nishizaka and colleagues dissect the events that occur within each 120-degree discrete step in the rotation of the ATP synthase during ATP hydrolysis. They show that ATP binding to one of three sites in the synthase induces an 80-degree rotation and may trigger hydrolysis of a previously bound ATP molecule in the neighboring site. Release of the hydrolyzed nucleotide at the neighboring site induces the next 40-degree rotation to complete the 120-degree step observed in previous studies.