The Peripheral Stalk of Rotary ATPases

Abstract

Rotary ATPases are a family of enzymes that are thought of as molecular nanomotors and are classified in three types: F, A, and V-type ATPases. Two members (F and A-type) can synthesize and hydrolyze ATP, depending on the energetic needs of the cell, while the V-type enzyme exhibits only a hydrolytic activity. The overall architecture of all these enzymes is conserved and three main sectors are distinguished: a catalytic core, a rotor and a stator or peripheral stalk. The peripheral stalks of the A and V-types are highly conserved in both structure and function, however, the F-type peripheral stalks have divergent structures. Furthermore, the peripheral stalk has other roles beyond its stator function, as evidenced by several biochemical and recent structural studies. This review describes the information regarding the organization of the peripheral stalk components of F, A, and V-ATPases, highlighting the key differences between the studied enzymes, as well as the different processes in which the structure is involved.

Mitochondrial F-ATP Synthase and Its Transition into an Energy-Dissipating Molecular Machine

“…In its simplest bacterial form, the F O sector consists of 9-15 copies of the subunit c , two copies of the subunit b , and a copy of the subunit a [14]. While the b subunits constitute part of the peripheral stalk [15], the subunit a is embedded in the membrane, where it is organized into a four-helix horizontal bundle that wraps around the c -ring, forming two semichannels through which the H + flow by protonation/deprotonation of conserved carboxylic residues present in each c subunit [16–18]. The eukaryotic F O sector is made up of subunits A6L, e , f , and g and 2 or 3 other additional subunits (DAPIT and 6.8PL in vertebrates; i / j , k , and l in yeast), besides subunits a , b , and c [14].…”

“…The peripheral stalk tends to diverge throughout evolution, even though the overall structure seems to be constant [15]. The bacterial peripheral stalk consists of the b 2 dimer, which spans the whole enzyme, and a single copy of the subunit δ .…”

Structural Asymmetry and Kinetic Limping of Single Rotary F-ATP Synthases

“…The F O and F 1 domains are also connected by a peripheral, eccentric stalk. In eubacteria, this stalk is composed of a homodimer of b subunits that forms a right-handed coiled-coil [30,31,32], which is tethered to the δ subunits, and docks to subunit a that serves as the interface with the c 10 -ring. Subunit δ binds to the N-termini of all α subunits at the top of the F 1 -head.…”

Reversible Thiol Oxidation Inhibits the Mitochondrial ATP Synthase in Xenopus laevis Oocytes

“…Alternatively, a negative charge may electrostatically repel dimer interfaces. Thiols in subunit e and g also regulate the stability and formation of oligomers, which dictate inner mitochondrial membrane topology [74][75][76]. For example, F 1 -F o ATP synthase dimers shape cristae to create an efficient proton sink for ATP synthesis [77].…”