Subunit composition of ATP synthase

SUBUNIT COMPOSITION OF ATP SYNTHASE

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ATP synthase has two major structural parts known as F₁ and F_o 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 j and k (formerly known as 6.8 PL (6.8 kD proteolipid) and DAPIT (diabetes associated protein in insulin sensitive tissue)) [5] [6], and fungal enzymes, supernumerary subunits j, k and l [7]. Subunit l is closely related to subunit k. 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 c-ring and subunits γ, δ and ε, turns. Passage of protons through a pathway between the c-ring and subunit a releases energy to drive the clockwise rotation of the rotor (as viewed from the membrane) during ATP synthesis. The c₈-ring found in the bovine and human enzymes probably persists throughout metazoans [8] [9]. S. cerevisiae and Pichia angusta have c10-rings [10]. The functions of subunits e, f, g, DAPIT and 6.8PL are becoming less obscure as the resolution and accuracy of cryo-em structures of dimeric ATPases improve. [11]. 

The subunit compositions of bacterial and chloroplast ATP synthases are simpler than those from mitochondria [12] [13] [14], 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 [15]. The bacterial δ-subunit is the orthologue of the mitochondrial OSCP [15] 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 mycobacteria, the δ- and b-subunits are fused. The number of c-subunits in the c-rings in bacterial ATP synthases varies from 9-17 [16] [17] [18].

REFERENCES

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