Regulatory Mechanisms of Proton-Translocating FOF1-ATP Synthase

Abstract

H(+)-F(O)F(1)-ATP synthase catalyzes synthesis of ATP from ADP and inorganic phosphate using the energy of transmembrane electrochemical potential difference of proton (deltamu(H)(+). The enzyme can also generate this potential difference by working as an ATP-driven proton pump. Several regulatory mechanisms are known to suppress the ATPase activity of F(O)F(1): 1. Non-competitive inhibition by MgADP, a feature shared by F(O)F(1) from bacteria, chloroplasts and mitochondria 2. Inhibition by subunit epsilon in chloroplast and bacterial enzyme 3. Inhibition upon oxidation of two cysteines in subunit gamma in chloroplast F(O)F(1) 4. Inhibition by an additional regulatory protein (IF(1)) in mitochondrial enzyme In this review we summarize the information available on these regulatory mechanisms and discuss possible interplay between them.

Regulation of the F1F0-ATP Synthase Rotary Nanomotor in its Monomeric-Bacterial and Dimeric-Mitochondrial Forms

“…In agreement with this work, the structure of the γ-ε domain in the E. coli F 1 -ATP synthase [25] was found very similar to that of the isolated subunits [18]. Furthermore, it has been found that the ratchet mechanism of ε can be regulated by ATP binding in some bacteria [9,26]. When ATP is bound, the closed conformation is stabilized, thus favoring rotation of the central stalk in the ATPase direction; conversely, at low ATP concentrations, ε is unable to bind ATP, and therefore the extended conformation is favored, thus leaving the enzyme prone to rotate into the ATP synthase turnover.…”

“…The coupling between F 1 and F 0 is critical for efficient ATP synthesis to occur and major progress in the understanding of this coupling mechanism has been achieved. Several approaches at different laboratories showed that a central rotor actually gyrates relative to a stator that holds the catalytic subunits; this rotation induces the alternating binding, catalysis, and product release from three catalytic sites of F 1 (for reviews, see [5][6][7][8][9]). These studies also indicated that the γ subunit, together with ε and the ring of 9-15 c subunits of F 0 , form the rotor in the central part of the enzyme.…”

ATP Hydrolysis and Synthesis of a Rotary Motor V-ATPase from Thermus thermophilus

“…In addition the F 1 portion of F 0 F 1 can synthesize ATP when the rotor shaft is forced to rotate in a direction opposite that of ATP hydrolysis (11,12). It is well known that the ATP hydrolysis reaction catalyzed by both V-ATPase and F 0 F 1 is highly regulated by a number of different mechanisms to prevent wasteful ATP consumption (1,13). One such mechanism is Mg-ADP inhibition, whereby Mg-ADP binds into the catalytic site of the V 1 and F 1 domains and thus inhibits ATP hydrolysis (14 -17).…”

The Regulatory C-Terminal Domain of Subunit ε of F o F 1 ATP Synthase Is Dispensable for Growth and Survival of Escherichia coli

“…Subunit ε in bacterial F o F 1 has been known to be an intrinsic inhibitor of F 1 and F o F 1 complex (18,21,23) and is proposed to have a regulatory function (10,11,42). Although the inhibitory effects of subunit ε vary among species, in general, ε inhibits ATP hydrolysis activity while repressing ATP synthesis activity to a lesser degree (14,27).…”