19.11:
ATP Synthase: Structure
ATP synthase is a membrane-bound biological nanomotor, primarily known for converting ADP and inorganic phosphate to ATP.
This enzyme is powered by an electrochemical gradient, established by protons distributed unevenly across the membrane.
The protons flow down their electrochemical gradient and activate the two functional domains of ATP synthase: the F0-subcomplex and the F1-subcomplex.
F0 is a transmembrane component with subunits that interact directly with the protons.
First, the stator-subunit enables protons to enter through its channels and attach to the binding site on another subunit called the rotor.
The binding of the incoming protons causes the rotor to spin. When protons complete a 360-degree full rotation, they dissociate from the rotor and exit the membrane through another stator-channel.
These dynamic movements within ATP synthase are stabilized by a peripheral stalk that establishes a rigid connection between the F0 and the F1 subcomplexes.
19.11:
ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP synthases are classified as F (Phosphorylation factor), V (Vacuole), A (Archaea), P (Proton), or E (Extracellular). The mammalian ATP synthase is also known as the complex five of the respiratory chain complexes in the inner mitochondrial membrane.
It has been estimated that an average adult body produces 40 kg of ATP every day. Therefore, ATP synthesis is one of the most crucial and frequent processes that occur in the body.
Any mutation or defects in the ATP synthase enzyme can lead to fatal diseases. Mutation in one or more subunits of ATP synthase can inhibit their assembly into a functional enzyme. Consequently, this can lead to congenital defects such as cardiomyopathy, hepatomegaly, and lactic acidosis, causing the death of a newborn. Further, a mutation in the α subunit has been associated with several pathologies including, retinitis pigmentosa, neuropathy, familial bilateral striatal necrosis, and one type of Leigh syndrome, which is a neuromuscular disorder in young children. Also, the reduced expression of the β subunit and accumulation of α subunit in the cytosol can cause Alzheimer's disease.
Suggested Reading
- Baldo, Manuela Schubert, and Laura Vilarinho. "Molecular basis of Leigh syndrome: a current look." Orphanet journal of rare diseases 15, no. 1 (2020): 1-14.
- Neupane, Prashant, Sudina Bhuju, Nita Thapa, and Hitesh Kumar Bhattarai. "ATP synthase: structure, function and inhibition." Biomolecular Concepts 10, no. 1 (2019): 1-10.