The peripheral stalk of the mitochondrial ATP synthase

Abstract

The peripheral stalk of F-ATPases is an essential component of these enzymes. It extends from the membrane distal point of the F 1 catalytic domain along the surface of the F 1 domain with subunit a in the membrane domain. Then, it reaches down some 45 Å to the membrane surface, and traverses the membrane, where it is associated with the a-subunit. Its role is to act as a stator to hold the catalytic α 3β 3 subcomplex and the a-subunit static relative to the rotary element of the enzyme, which consists of the c-ring in the membrane and the attached central stalk. The central stalk extends up about 45 Å from the membrane surface and then penetrates into the α 3β 3 subcomplex along its central axis. The mitochondrial peripheral stalk is an assembly of single copies of the oligomycin sensitivity conferral protein (the OSCP) and subunits b, d and F 6. In the F-ATPase in Escherichia coli, its composition is simpler, and it consists of a single copy of the δ-subunit with two copies of subunit b. In some bacteria and in chloroplasts, the two copies of subunit b are replaced by single copies of the related proteins b and b′ (known as subunits I and II in chloroplasts). As summarized in this review, considerable progress has been made towards establishing the structure and biophysical properties of the peripheral stalk in both the mitochondrial and bacterial enzymes. However, key issues are unresolved, and so our understanding of the role of the peripheral stalk and the mechanism of synthesis of ATP are incomplete.