The v-ATPase, also known as vacuolar-type ATPase, is a multisubunit enzyme complex found in the membranes of various cellular compartments, including lysosomes, endosomes, Golgi apparatus, and secretory vesicles. It plays a crucial role in the regulation of intracellular pH and the acidification of these compartments.
The v-ATPase is composed of two main domains: the V1 domain, located in the cytosol, and the V0 domain, embedded in the membrane.
The V1 domain is responsible for ATP hydrolysis, while the V0 domain functions as a proton pump.
The V1 domain consists of eight different subunits (A-H), which form a peripheral complex resembling a rotary motor. Subunits A and B are involved in ATP hydrolysis, whereas subunits C, D, and E are involved in ATP binding and subunit assembly. Subunits F, G, and H are regulatory subunits that participate in the assembly and regulation of the complex.
The V0 domain consists of another set of subunits (a, c, c', c", d, and e), which are integral membrane proteins. Subunit a is involved in proton translocation, while the c subunits form a ring-like structure that transports protons across the membrane. Subunits d and e are required for the stability and assembly of the complex.
Sun-Wada & Wada (2015), BBA
The v-ATPase functions primarily as a proton pump, using the energy derived from ATP hydrolysis to transport protons (H+) across the membrane against their concentration gradient. This process leads to the acidification of the compartment, creating an acidic environment necessary for various cellular processes. Some important functions of the v-ATPase include:
Collins & Forgac (2020), BBA
The activity of the v-ATPase can be regulated through multiple mechanisms. One key regulatory mechanism involves reversible disassembly and reassembly of the V1 and V0 domains, which modulates the proton pump activity. Additionally, various factors such as pH, ATP availability, post-translational modifications, and binding of regulatory proteins can influence its activity.
Video from Rubinstein Laboratory @rubinsteinlaboratory2935
V-ATPase is a crucial enzyme complex responsible for proton pumping and acidification of cellular compartments. Its diverse functions make it essential for numerous cellular processes, including protein trafficking, neurotransmitter release, and pH regulation.
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