Abstract
The vacuolar (H+)-ATPases (or V-ATPases) are ATP-dependent proton pumps that function both to acidify intracellular compartments and to transport protons across the plasma membrane. Acidification of intracellular compartments is important for such processes as receptor-mediated endocytosis, intracellular trafficking, protein processing, and coupled transport. Plasma membrane V-ATPases function in renal acidification, bone resorption, pH homeostasis, and, possibly, tumor metastasis. This review will focus on work from our laboratories on the V-ATPases from mammalian clathrin-coated vesicles and from yeast. The V-ATPases are composed of two domains. The peripheral V1 domain has a molecular mass of 640 kDa and is composed of eight different subunits (subunits A–H) of molecular mass 70–13 kDa. The integral V0 domain, which has a molecular mass of 260 kDa, is composed of five different subunits (subunits a, d, c, c', and c”) of molecular mass 100–17 kDa. The V1 domain is responsible for ATP hydrolysis whereas the V0 domain is responsible for proton transport. Using a variety of techniques, including cysteine-mediated crosslinking and electron microscopy, we have defined both the overall shape of the V-ATPase and the V0 domain as well as the location of various subunits within the complex. We have employed site-directed and random mutagenesis to identify subunits and residues involved in nucleotide binding and hydrolysis, proton translocation, and the coupling of these two processes. We have also investigated the mechanism of regulation of the V-ATPase by reversible dissociation and the role of different subunits in this process.
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Inoue, T., Wilkens, S. & Forgac, M. Subunit Structure, Function, and Arrangement in the Yeast and Coated Vesicle V-ATPases. J Bioenerg Biomembr 35, 291–299 (2003). https://doi.org/10.1023/A:1025720713747
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DOI: https://doi.org/10.1023/A:1025720713747