InterPro: IPR020537 ATPase, F0 complex, subunit C, DCCD-binding site

ATPases (or ATP synthases) are membrane-bound enzyme complexes/ion transporters that combine ATP synthesis and/or hydrolysis with the transport of protons across a membrane. ATPases can harness the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. Some ATPases work in reverse, using the energy from the hydrolysis of ATP to create a proton gradient. There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport [1, 2].

• F-ATPases (F1F0-ATPases) in mitochondria, chloroplasts and bacterial plasma membranes are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
• V-ATPases (V1V0-ATPases) are primarily found in eukaryotic vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles.
• A-ATPases (A1A0-ATPases) are found in Archaea and function like F-ATPases.
• P-ATPases (E1E2-ATPases) are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
• E-ATPases are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.

F-ATPases (also known as F1F0-ATPase, or H(+)-transporting two-sector ATPase) (EC:3.6.3.14) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), nine in mitochondria (A-G, F6, F8). Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [3]. These ATPases can also work in reverse to hydrolyse ATP to create a proton gradient.

Subunit C (also called subunit 9, or proteolipid) is found in the F0 complex of F-ATPases. Ten C subunits form an oligomeric ring that makes up the F0 rotor. The flux of protons through the ATPase channel drives the rotation of the C subunit ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the C subunit ring of F0. The sequential protonation and deprotonation of Asp61 of subunit C is coupled to the stepwise movement of the rotor [4].

Structurally, subunit c consists of two long terminal hydrophobic regions, which probably span the membrane, and a central hydrophilic region. N,N'-dicyclohexylcarbodiimide (DCCD) can bind covalently to subunit c and thereby abolish the ATPase activity. DCCD binds to a specific glutamate or aspartate residue which is located in the middle of the second hydrophobic region near the C terminus of the protein. This entry represents the site that includes the DCCD-binding residue.