Regulation of the F0F1-ATP synthase:: The conformation of subunit ε might be determined by directionality of subunit γ rotation

F0F1-ATP synthase couples ATP synthesis/hydrolysis with transmembrane proton transport. The catalytic mechanism involves rotation of the gamma epsilon(similar to 10)-subunits complex relative to the rest of the enzyme. In the absence of protonmotive force the enzyme is inactivated by the tight binding of MgADP. Subunit F also modulates the activity: its conformation can change from a contracted to extended form with C-terminus stretched towards F-1. The latter form ihnibits ATP hydrolysis (but not synthesis). We propose that the directionality of the coiled-coil subunit gamma rotation determines whether subunit E is in contracted or extended form. Block of rotation by MgADP presumably induces the extended conformation of subunit F. This conformation might serve as a safety lock, stabilizing the ADP-inhibited state upon de-energization and preventing spontaneous re-activation and wasteful ATP hydrolysis. The hypothesis merges the known regulatory effects of ADP, protonmotive force and conformational changes of subunit epsilon into a consistent picture. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.