Subunit composition


ATP synthase has two major structural parts known as F1 and Fo linked by the peripheral and central stalks. The F1 catalytic domain of the mitochondrial enzyme is a globular assembly of five different proteins α, β, γ, δ and ε with the stoichiometry 3:3:1:1:1 [1]. The three α-subunits and the three β-subunits are arranged alternately around a central α-helical coiled-coil in the γ-subunit. The γ-subunit protrudes from α3β3-subcomplex and the δ- and ε-subunits are associated with its foot. The foot interacts with a ring of c subunits in the membrane domain. The Fo domain is an assembly of single copies of each of the ATP6 (or a), b, c, e, f, g, and ATP8 (or A6L) subunits, all of them embedded in the inner mitochondrial membrane [2][3][4]. Mammalian enzymes contain additional supernumerary subunits DAPIT and 6.8 proteolipid [5][6], and fungal enzymes, supernumerary subunits j, k and l [7].  The peripheral stalk (made of single copies of subunits OSCP, b, d and F6), the a subunit and the associated supernumerary subunits constitute the enzyme’s "stator", against which the rotor made of the central stalk (subunits γ, δ and ε) and the associated c-ring turns. The proton pathway lies between the c-ring and subunit ATP6 (or a). Passage of protons through this pathway releases energy to drive the clockwise rotation of the rotor (as viewed from the membrane) during ATP synthesis. The c8-ring found in bovine and human enzymes probably persists throughout metazoans [8][9].  S. cerevisiae and Pichia angusta have c10-rings [10][11].  The functions of subunits e, f, g, DAPIT and 6.8 proteolipid are obscure, but the yeast orthologue of subunit e is involved in formation of dimers of the ATP synthase complex. DAPIT stands for “diabetes associated protein in insulin-sensitive tissues” [12]

The subunit compositions of bacterial and chloroplast ATP synthases are simpler than those from mitochondria [13][14][15], and the complexes are monomeric. The F1 catalytic domain consists of the α3β3-subcomplex plus the central stalk made of single copies of subunits γ and ε. The bacterial or chloroplast ε-subunit is the orthologue of the mitochondrial δ-subunit [16]. The bacterial δ-subunit is the orthologue of the mitochondrial OSCP [16] and forms part of the peripheral stalk which contains either two identical copies of the b-subunit (as in Escherichia coli for example), or a single copy of the b-subunit plus one copy of a related b’-subunit, each with a single transmembrane α-helix (as in chloroplasts and Paracoccus denitrificans, for example). Mitochondrial and bacterial peripheral stalk subunits have no obvious relationships between their sequences, and the peripheral stalks are the most divergent regions among the common domains of the ATP synthases. In the mycobacteria, the δ- and b-subunits are fused. The number of c-subunits in the c-rings in bacteria ATP synthases varies from 9-15 [17][18][19].


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