ATP synthase

ATP synthase is an enzyme that creates the energy storage molecule adenosine triphosphate (ATP). ATP is the most commonly used 'energy currency' of cells for all organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi). The overall reaction catalyzed by ATP synthase is: ATP synthase is an enzyme that creates the energy storage molecule adenosine triphosphate (ATP). ATP is the most commonly used 'energy currency' of cells for all organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi). The overall reaction catalyzed by ATP synthase is: The formation of ATP from ADP and Pi is energetically unfavorable and would normally proceed in the reverse direction. In order to drive this reaction forward, ATP synthase couples ATP synthesis during cellular respiration to an electrochemical gradient created by the difference in proton (H+) concentration across the mitochondrial membrane in eukaryotes or the plasma membrane in bacteria. During photosynthesis in plants, ATP is synthesized by ATP synthase using a proton gradient created in the thylakoid lumen through the thylakoid membrane and into the chloroplast stroma. ATP synthase consists of two main subunits, FO and F1, which has a rotational motor mechanism allowing for ATP production. Because of its rotating subunit, ATP synthase is a molecular machine. The F1 fraction derives its name from the term 'Fraction 1' and FO (written as a subscript letter 'o', not 'zero') derives its name from being the binding fraction for oligomycin, a type of naturally-derived antibiotic that is able to inhibit the FO unit of ATP synthase. These functional regions consist of different protein subunits — refer to tables. This enzyme is used in synthesis of ATP through aerobic respiration. Located within the thylakoid membrane and the inner mitochondrial membrane, ATP synthase consists of two regions FO and F1. FO causes rotation of F1 and is made of c-ring and subunits a, b, d, F6. F1 is made of α , β , γ , δ {displaystyle alpha ,eta ,gamma ,delta } subunits. F1 has a water-soluble part that can hydrolyze ATP. FO on the other hand has mainly hydrophobic regions. FO F1 creates a pathway for protons movement across the membrane. The F1 portion of ATP synthase is hydrophilic and responsible for hydrolyzing ATP. The F1 unit protrudes into the mitochondrial matrix space. Subunits α {displaystyle alpha } and β {displaystyle eta } make a hexamer with 6 binding sites. Three of them are catalytically inactive and they bind ADP. Other three subunits catalyze the ATP synthesis. The other F1 subunits γ , δ , ϵ {displaystyle gamma ,delta ,epsilon } are a part of a rotational motor mechanism. γ {displaystyle gamma } subunit allows β {displaystyle eta } to go through conformational changes, i.e. closed, half open and open states allows for ATP to be bound and released once synthesized. The F1 particle is large and can be seen in the transmission electron microscope by negative staining. These are particles of 9 nm diameter that pepper the inner mitochondrial membrane. FO is a water insoluble protein with eight subunits and a transmembrane ring. The ring has a tetramer shape with a helix loop helix protein that goes though conformational changes when protonated and deprotonated, pushing neighboring subunits to rotate, causing the spinning of FO which then also affects conformation of F1, resulting in switching of states of alpha and beta subunits. The FO region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits, a, b, and c, and (in humans) six additional subunits, d, e, f, g, F6, and 8 (or A6L). An atomic model for the dimeric yeast FO region was determined by cryo-EM at an overall resolution of 3.6 Å. This part of the enzyme is located in the mitochondrial inner membrane and couples proton translocation to the rotation the causes ATP synthesis in the F1 region. In the 1960s through the 1970s, Paul Boyer, a 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 MRC Laboratory of Molecular Biology 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, in essence, correct. For elucidating this, Boyer and Walker shared half of the 1997 Nobel Prize in Chemistry.