Editing ATP synthase (section)

== Binding model ==
[[File:ATPsyn.gif|thumb|220px|right|Mechanism of ATP synthase. ADP and P<sub>i</sub> (pink) shown being combined into ATP (red), while the rotating γ (gamma) subunit in black causes conformational change.]]
[[File:ATP-Synthase.svg|thumb|230px|Depiction of ATP synthase using the [[Chemiosmosis|chemiosmotic]] proton gradient to power ATP synthesis through [[oxidative phosphorylation]].]]
In the 1960s through the 1970s, [[Paul D. Boyer|Paul Boyer]], a [[University of California, Los Angeles|UCLA]] Professor, developed the binding change, or flip-flop, mechanism theory, which postulated that ATP synthesis is dependent on a conformational change in ATP synthase generated by rotation of the gamma subunit. The research group of [[John E. Walker]], then at the [[Laboratory of Molecular Biology|MRC Laboratory of Molecular Biology]] in [[Cambridge]], crystallized the F<sub>1</sub> catalytic-domain of ATP synthase. The structure, at the time the largest asymmetric protein structure known, indicated that Boyer's rotary-catalysis model was, in essence, correct. For elucidating this, Boyer and Walker shared half of the 1997 [[Nobel Prize in Chemistry]].

The crystal structure of the F<sub>1</sub> showed alternating alpha and beta [[Protein subunit|subunits]] (3 of each), arranged like segments of an orange around a rotating asymmetrical gamma subunit. According to the current model of ATP synthesis (known as the alternating catalytic model), the transmembrane potential created by (H+) proton cations supplied by the electron transport chain, drives the (H+) proton cations from the intermembrane space through the membrane via the F<sub>O</sub> region of ATP synthase. A portion of the F<sub>O</sub> (the ring of [[ATP synthase subunit C|c-subunits]]) [[Rotating locomotion in living systems|rotates]] as the protons pass through the membrane. The [[ATP synthase subunit C|c-ring]] is tightly attached to the asymmetric central stalk (consisting primarily of the gamma subunit), causing it to rotate within the alpha<sub>3</sub>beta<sub>3</sub> of F<sub>1</sub> causing the 3 catalytic nucleotide binding sites to go through a series of conformational changes that lead to ATP synthesis. The major F<sub>1</sub> subunits are prevented from rotating in sympathy with the central stalk rotor by a peripheral stalk that joins the alpha<sub>3</sub>beta<sub>3</sub> to the non-rotating portion of F<sub>O</sub>. The structure of the intact ATP synthase is currently known at low-resolution from [[electron cryo-microscopy]] (cryo-EM) studies of the complex. The cryo-EM model of ATP synthase suggests that the peripheral stalk is a flexible structure that wraps around the complex as it joins F<sub>1</sub> to F<sub>O</sub>. Under the right conditions, the enzyme reaction can also be carried out in reverse, with ATP hydrolysis driving [[proton pump]]ing across the membrane.

The binding change mechanism involves the active site of a β subunit's cycling between three states.<ref name=Gresser>{{cite journal | vauthors = Gresser MJ, Myers JA, Boyer PD | title = Catalytic site cooperativity of beef heart mitochondrial F<sub>1</sub> adenosine triphosphatase. Correlations of initial velocity, bound intermediate, and oxygen exchange measurements with an alternating three-site model | journal = The Journal of Biological Chemistry | volume = 257 | issue = 20 | pages = 12030–12038 | date = October 1982 | pmid = 6214554 | doi = 10.1016/S0021-9258(18)33672-X | doi-access = free }}</ref> In the "loose" state, ADP and phosphate enter the active site; in the adjacent diagram, this is shown in pink. The enzyme then undergoes a change in shape and forces these molecules together, with the active site in the resulting "tight" state (shown in red) binding the newly produced ATP molecule with very high [[Dissociation constant|affinity]]. Finally, the active site cycles back to the open state (orange), releasing ATP and binding more ADP and phosphate, ready for the next cycle of ATP production.<ref name=Nakamoto>{{cite journal | vauthors = Nakamoto RK, Baylis Scanlon JA, Al-Shawi MK | title = The rotary mechanism of the ATP synthase | journal = Archives of Biochemistry and Biophysics | volume = 476 | issue = 1 | pages = 43–50 | date = August 2008 | pmid = 18515057 | pmc = 2581510 | doi = 10.1016/j.abb.2008.05.004 }}</ref>