An ATP synthase (EC 3.6.3.14) 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: The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... Adenosine diphosphate, abbreviated ADP, is a nucleotide. ... Above is a ball-and-stick model of the inorganic hydrogenphosphate anion (HPO42−). Colour coding: P (orange); O (red); H (white). ...

ADP + P_i → ATP

Molecular model of ATP synthase by X-ray diffraction method

ATP synthase in E. coli

These enzymes are of crucial importance in almost all organisms, because ATP is the common "energy currency" of cells. Image File history File links Download high-resolution version (1200x1600, 1522 KB) I, the creator of this work, hereby grant the permission to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1. ... Image File history File links Download high-resolution version (1200x1600, 1522 KB) I, the creator of this work, hereby grant the permission to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1. ... Image File history File links Atpsynthase_nobelfoundation. ... Image File history File links Atpsynthase_nobelfoundation. ... E. coli redirects here. ...

In mitochondria, the F₁F_O 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 nomenclature of the enzyme suffers from a long history. The F₁ fraction derives it name from the term "Fraction 1" and F_O (written as a subscript "O", not "zero") derives it name from being the oligomycine binding fraction. Taking as an example the nomenclature of subunits in the bovine enzyme, many subunits have Greek and Roman alphabet names (alpha, beta, gamma, delta, epsilon and a, b, c, d, e, f, g, h), while others have more complex names such as F₆ (from "Fraction 6"), OSCP (the oligomycin sensitivity conferral protein), A6L (named for the gene that codes for it in the mitochondrial genome) and IF1 (inhibitory factor 1). In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ...

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. A submitochondrial particle is a compartmentalized membranous product of exposing mitochondria to ultrasound. ...

The antibiotic oligomycin inhibits ATP synthase. Oligomycins are macrolides created by Streptomyces that can be poisonous to other organisms. ...

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-catalysis model was essentially correct. For elucidating this Boyer and Walker shared half of the 1997 Nobel Prize in Chemistry. Jens Christian Skou received the other half of the Chemistry prize that year "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase" Paul Delos Boyer (born July 31, 1918) is an American biochemist. ... John Ernest Walker (born January 7, 1941) is an English chemist who won the Nobel Prize in Chemistry in 1997. ... 1997 (MCMXCVII) was a common year starting on Wednesday of the Gregorian calendar. ... This is a list of Nobel Prize laureates in Chemistry from 1901 to 2006. ... Jens Christian Skou (born October 8, 1918) is a Danish chemist and Nobel laureate. ...

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. In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or coassembles) with other protein molecules to form a multimeric or oligomeric protein. ... // Properties [1][2] In physics, the proton (Greek proton = first) is a subatomic particle with an electric charge of one positive fundamental unit (1. ... Electron cryomicroscopy (aka cryo-electron microscopy) is a developing method in structural biology. ...

Physiological role

Like all enzymes, the activity of F₁F_O ATP synthase is reversible. 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. // Properties [1][2] In physics, the proton (Greek proton = first) is a subatomic particle with an electric charge of one positive fundamental unit (1. ... Horizontal line (use sparingly)d grade for the grade or gradient of roads and other geographic features. ... A flagellum (plural, flagella) is a whip-like organelle that many unicellular organisms, and some multicellular ones, use to move about. ...

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. The same process takes place in mitochondria, where ATP synthase is located in the inner mitochondrial membrane (so that F₁-part sticks into mitochondrial matrix, where ATP synthesis takes place). Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... Electrochemical potential is a thermodynamic measure that reflects energy from entropy and electrostatics and is typically invoked in molecular processes that involve diffusion. ... The electron transfer chain (also called the electron transport chain, ETC, e-train, or simply electron transport), is any series of protein complexes and lipid-soluble messengers that convert the reductive potential of energized electrons into a cross-membrane proton gradient. ... The Electron Transport Chain. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ...

ATP synthase in different organisms

Plant ATP synthase

In plants ATP synthase is also present in chloroplasts (CF₁F_O-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. Chloroplasts are organelles found in plant cells and eukaryotic algae which conduct photosynthesis. ... Thylakoids (commonly referred to as Thylakoid membranes) are a phospholipid bilayer membrane-bound compartment internal to chloroplasts, and represent the majority of its internal structure. ... Stroma can refer to: The connective supportive framework of a biological cell, tissue, or organ. ... Overview of the Calvin cycle and carbon fixation The Calvin cycle (or Calvin-Benson cycle or carbon fixation) is a series of biochemical reactions that takes place in the stroma of chloroplasts in photosynthetic organisms. ... Chloroplasts are organelles found in plant cells and eukaryotic algae which conduct photosynthesis. ... Electrochemical potential is a thermodynamic measure that reflects energy from entropy and electrostatics and is typically invoked in molecular processes that involve diffusion. ...

E. coli ATP synthase

E. coli ATP synthase is the simplest known form of ATP synthase, with 8 different subunit types.

Yeast ATP synthase

Yeast ATP synthase is the most complex known and is made of 20 different types of subunits.

Evolution of ATP synthase

The evolution of ATP synthase is thought to be an example of modular evolution, where two subunits with their own functions have become associated and gained new functionality. The F_O particle shows significant similarity to hexemeric DNA helicases and the F₁ particle shows some similarity to H⁺ powered flagellar motor complexes. For a non-technical introduction to the topic, please see Introduction to evolution. ... Helicase is an enzyme vital to all living organisms. ...

The α₃β₃ hexamer of the F_O particle shows significant structural similarity to hexameric DNA helicases; both form a ring with 3 fold rotational symmetry with a central pore. Both also have roles dependent on the relative rotation of a macromolecule within the pore; the DNA helicases use the helical shape of DNA to drive their motion along the DNA molecule and to detect supercoiling whilst the α₃β₃ hexamer uses the conformational changes due rotation of the γ subunit to drive an enzymatic reaction.

The H⁺ motor of the F₁ particle shows great functional similarity to the H⁺ motors seen in flagellar motors. Both feature a ring of many small alpha helical proteins which rotate relative to nearby stationary proteins using a H⁺ potential gradient as an energy source. This is, however, a fairly tenuous link - the overall structure of flagellar motors is far more complex than the F₁ particle and the ring of rotating proteins is far larger, with around 30 compared to the 10, 11 or 14 known in the F₁ complex.

The modular evolution theory for the origin of ATP synthase suggests that two subunits with independent function, a DNA helicase with ATPase activity and a H⁺ motor, were able to bind, and the rotation of the motor drive the ATPase activity of the helicase in reverse. This would then evolve to become more efficient, and eventually develop into the complex ATP synthases seen today. Alternatively the DNA helicase/H⁺ motor complex may have had H⁺ pump activity, the ATPase activity of the helicase driving the H⁺ motor in reverse. This could later evolve to carry out the reverse reaction and act as an ATP synthase.

See also

• mitochondrion
• chloroplast
• electron transfer chain
• proton pump
• transmembrane ATPase
• Flavo Protein

Electron micrograph of a mitochondrion showing its mitochondrial matrix and membranes In cell biology, a mitochondrion (plural mitochondria) (from Greek μιτος or mitos, thread + κουδριον or khondrion, granule) is a membrane-enclosed organelle, found in most eukaryotic cells. ... Chloroplasts are organelles found in plant cells and eukaryotic algae that conduct photosynthesis. ... The electron transfer chain (also called the electron transport chain, ETC, e-train, or simply electron transport), is any series of protein complexes and lipid-soluble messengers that convert the reductive potential of energized electrons into a cross-membrane proton gradient. ... A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment, thereby creating a difference or gradient in both pH and electrical charge (ignoring differences in buffer capacity) and tending to establish an electrochemical potential. ... ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. ... Flavo Protein is, as you can infer from the name, a protein. ...

External links

• "ATP synthase - a splendid molecular machine"
• Well illustrated ATP synthase lecture by Antony Crofts of the University of Illinois at Urbana-Champaign.