Pathways & interactions
ATP synthase, F1 complex, epsilon subunit, mitochondrial (IPR006721)
Short name: ATP_synth_F1_esu_mt
Overlapping homologous superfamilies
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing 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.
There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [PMID: 15473999, PMID: 15078220]. The different types include:
- F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
- V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [PMID: 20450191]. They are also found in bacteria [PMID: 9741106].
- A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [PMID: 18937357, PMID: 1385979].
- P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
- E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.
F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (EC:126.96.36.199) 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), with additional subunits in mitochondria. 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 [PMID: 11309608]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.
This family constitutes the mitochondrial ATP synthase epsilon subunit, which is distinct from the bacterial epsilon subunit (the latter being homologous to the mitochondrial delta subunit, IPR001469). The mitochondrial epsilon subunit is located in the stalk region of the F1 complex, and acts as an inhibitor of the ATPase catalytic core. The epsilon subunit can assume two conformations, contracted and extended, where the latter inhibits ATP hydrolysis. The conformation of the epsilon subunit is determined by the direction of rotation of the gamma subunit, and possibly by the presence of ADP. The extended epsilon subunit is thought to become extended in the presence of ADP, thereby acting as a safety lock to prevent wasteful ATP hydrolysis [PMID: 16154570].
In Drosophila, the protein Stunted which activates the G-protein coupled receptor Methuselah in vitro, leading to increased intracellular calcium ion levels, is embryonically lethal [PMID: 19672878, PMID: 15133470].