ATP synthase

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An ATP synthase (Template:EC number) is a general term for an enzyme that can synthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate by utilizing some form of energy. The overall reaction sequence is:

ADP + P_i → ATP

Image:Atpsynthase nobelfoundation.jpg

These enzymes are of crucial importance in almost all organisms, because ATP is the common "energy currency" of cells.

In mitochondria, the F_OF₁ ATP synthase has a long history of scientific study. The F₁ portion of the ATP synthase is above the membrane, the F_O portion is within the membrane. It's easy to visualize the F_OF₁ particle as resembling the fruiting body of a common mushroom, with the head being the F₁ particle, the stalk being the gamma subunit of F₁, and the base and "roots" being the F_O particle embedded in the membrane. The F₁ particle was first isolated by Ephraim Racker in 1961.

The F₁ particle is large and can be seen in the transmission electron microscope by negative staining (1962, Fernandez-Moran et al., Journal of Molecular Biology, Vol 22, p 63). These are particles of 9 nm diameter that pepper the inner mitochondrial membrane. They were originally called elementary particles and were thought to contain the entire respiratory apparatus of the mitochondrion, but through a long series of experiments, Ephraim Racker and his colleagues were able to show that this particle is correlated with ATPase activity in uncoupled mitochondria and with the ATPase activity in submitochondrial particles created by exposing mitochondria to ultrasound. This ATPase activity was further associated with the creation of ATP by yet another long series of experiments in many laboratories.

The antibiotic oligomycin inhibits ATP synthase.

1 Binding change mechanism
2 Physiological role
3 Plant ATP synthase
4 E. coli ATP synthase
5 Yeast ATP synthase
6 See also
7 External links

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Binding change mechanism

In the 1960s through the 1970s, Paul Boyer developed his binding change, or flip-flop, mechanism, which postulated that ATP synthesis is coupled with a conformational change in the ATP synthase generated by rotation of the gamma subunit. The research group of John E. Walker, then at the MRC Laboratory of Molecular Biology in Cambridge but now at the MRC Dunn Human Nutrition Unit (also in Cambridge) crystallized the F₁ catalytic-domain of ATP synthase. The structure, at the time the largest asymmetric protein structure known, indicated that Boyer's rotary-cayalysis model was essentially correct. For elucidating this Boyer and Walker shared half of the 1997 Nobel Prize in Chemistry. Jens C Skou received the other half of the Chemistry prize that year "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase"

The crystal structure of the F₁ showed alternating alpha and beta subunits (3 of each), arranged like segments of an orange around an asymmetrical gamma subunit. 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 F_O region of ATP synthase. A portion of the F_O (the ring of c-subunits) rotates as the protons pass through the membrane. The c-ring is tightly attached to the asymmetric central stalk (consisting primarily of the gamma subunit) which rotates within the alpha₃beta₃ of F₁ causing the 3 catalytic nucleotide binding sites to go through a series of conformational changes that leads to ATP synthesis. The major F₁ subunits are prevented from rotating in sympathy with the central stalk rotor by a peripheral stalk that joins the alpha₃beta₃ to the non-rotating portion of F_O. 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 shows that the peripheral stalk is a flexible rope-like structure that wraps around the complex as it joins F₁ to F_O. Under the right conditions, the enzyme reaction can also be carried out in reverse, with ATP hydrolysis driving proton pumping across the membrane.

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Physiological role

The F₁F_O ATP synthase is a reversible enzyme. Large enough quantities of ATP cause it to create a transmembrane proton gradient, this is used by fermenting bacteria which do not have an electron transport chain, and hydrolyze ATP to make a proton gradient, which they use for flagella and transport of nutrients into the cell.

In respiring bacteria under physiological conditions, ATP synthase generally runs in the opposite direction, creating ATP while using the protonmotive force created by the electron transport chain as a source of energy. The overall process of creating energy in this fashion is termed oxidative phosphorylation. Same process takes place in mitochondria, were ATP synthase is located in the inner mitochondrial membrane (so that F₁-part sticks into mitochondrial matrix, were ATP synthesis takes place).

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Plant ATP synthase

In plants ATP synthase is also present in chloroplasts (CF_OF₁-ATP synthase). The enzyme is integrated into thylakoid membrane; the CF₁-part sticks into stroma, where dark reactions of photosynthesis (Also called the light-independent reactions or the Calvin cycle) and ATP synthesis take place. The overall structure and the catalytic mechanism of the chloroplast ATP synthase are almost the same as those of the mitochondrial enzyme. However, in chloroplasts the protonmotive force is generated not by respiratory electron transport chain, but by primary photosynthetic proteins - photosystems I and II and cytochrome b₆f.