COUPLING H-ATP SYNTHASES - GLIMPSES OF INTERACTING PARTS IN A DYNAMICMOLECULAR MACHINE( TRANSPORT AND ATP SYNTHESIS LN F1F0)

Reversible, F1F0-type ATPases (also termed F-ATP synthases) catalyze t he synthesis of ATP during oxidative phosphorylation, In animal cells, the enzyme traverses the inner mitochondrial membrane and uses the en ergy of an H+ electrochemical gradient, generated by electron transpor t, in coupling H+ translocation to ATP formation, Closely related enzy mes are found in the plasma membrane of bacteria such as Escherichia c oli, where the enzymes function reversibly depending upon nutritional circumstance. The F1F0-type enzymes are more distantly related to a se cond family of H+-translocating ATPases, the vacuolar-type or V-ATPase s, Recent structural information has provided important hints as to ho w these enzymes couple H+ transport to the chemical work of ATP synthe sis. The simplest F1F0-type enzymes, e.g. as in E. coli, are composed of eight types of submits in an unusual stoichiometry of alpha(3) beta (3) gamma delta epsilon (F-1) and a(1)b(2)c(12) (F-0). F-1 extends fro m the membrane, with the alpha and beta subunits alternating around a central subunit gamma. ATP synthesis occurs alternately in different b eta subunits, the cooperative tight binding of ADP+P-i at one catalyti c site being coupled to ATP release at a second, The differences in bi nding affinities appear to be caused by rotation of the gamma subunit in the center of the alpha(3) beta(3) hexamer. The gamma submit traver ses a 4.5 nm stalk connecting the catalytic submits to the membrane-tr aversing F-0 sector. Subunit c is the H+-translocating subunit of F-0. Protonation/deprotonation of Asp61 in the center of the membrane is c oupled to structural changes in an extramembranous loop of subunit c w hich interacts with both the gamma and epsilon subunits. Subunits gamm a and epsilon appear to move from one subunit c to another as ATP is s ynthesized, The torque of such movement is proposed to cause the rotat ion of gamma within the alpha(3) beta(3) complex, Four protons are tra nslocated for each ATP synthesized, The movement of gamma and epsilon therefore probably involves a unit of four c subunits, The organizatio n of subunits in F-0 remains a mystery; it will have to be understood if we are to understand the mechanism of torque generation.