Subunit rotation in F0F1-ATP synthases as a means of coupling proton transport through F-0 to the binding changes in F-1

The rotation of an asymmetric core of subunits in F0F1-ATP synthases has been proposed as a means of coupling the exergonic transport of protons through F-0 to the endergonic conformational changes in F-1 required for substrate binding and product release. Here we review earlier evidence both for and against subunit rotation and then discuss our most recent studies using reversible intersubunit disulfide cross-links to test for rotation. We conclude that the gamma subunit of F-1 rotates relative to the surrounding catalytic subunits during catalytic turnover by both soluble F-1 and membrane-bound F0F1. Furthermore, the inhibition of this rotation by the modification of F-0 with DCCD suggests that rotation in F-1 is obligatorily coupled to rotation in F-0 as an integral part of the coupling mechanism.