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After reading this article you will learn about the structure and mechanism of ATP synthase, with the help of suitable diagrams.
Boyer and Walker received the Nobel Prize in 1997 for elucidating the mechanism of ATP synthase. This is all-important reactions in which the proton-motive force, produced by proton translocation, is coupled to the synthesis of ATP from ADP and phosphate. ATP synthase is a complex structure consisting of two domains FO and F1. F1 is a spherical structure, sticks out into the matrix and is anchored to the membrane, consists of three α- and three β- subunits, all of which can bind nucleotides, but only the β-subunits can take part in the reactions (Fig. 4.54). FO is a cylindrical structure capable of rotation when driven by translocated protons and is linked to a central stalk that can revolve inside F1.
In F1FO ATP synthase, the FO portion is within the membrane and the F1 portion is above the membrane. The F1 fraction derives its name from the term “Fraction 1” and FO (written as a subscript “O”, not “zero”) derives its name from being the oligomycin binding fraction. The antibiotic oligomycin inhibits the FO unit of ATP synthase. A soluble portion, the F1 ATP-ase, contains 5 subunits, in a stoichiometry of 3α:3β:1γ:1δ:1ε. Three substrate binding sites are in the β-subunits (Fig. 4.55). Additional adenine nucleotide binding sites in α -subunits are regulatory.
According to the current model of ATP synthesis (known as the alternating catalytic model), the proton-motive force across the inner mitochondrial membrane, generated by the electron transport chain, drives the passage of protons through the membrane via the FO region of ATP synthase. A portion of the FO (the ring of C-subunits) rotates as the protons pass through the membrane. The erring is tightly attached to the asymmetric central stalk (consisting primarily of the gamma subunit) which rotates within the α3β3 of F1 causing the 3 catalytic nucleotide binding sites to go through a series of conformational changes that leads to ATP synthesis.
The mechanism that drives ATP synthesis seems to depend upon a binding charge conception in which catalytic sites on the β-subunits have different affinities for nucleotides and are designated loose (L), tight (T), and open (O). The loose (L) sites bind the substrates (ADP and phosphate) reversibly. The T sites then bind the reactants so tightly that ATP is formed. The O sites, which have a low affinity for substrates, then release the ATP already formed in the T state. The central stalk is driven by the retro-location of protons through FO (counter-clockwise, as seen from above), and rotates in 120° stages.
At each stage, each of the β-subunits in turn changes conformation: L changes to T (after binding ADP and phosphate), T to O, and O to L (after releasing ATP). The new L site then binds new ADP and phosphate and begins a new reaction sequence. One complete revolution of FO, therefore, results in the formation of 3 ATP, one from each of the β-subunits (~3.3 H+ needed for the formation of one ATP from ADP and Pi).
