Structure, subunit function and regulation of the coated vesicle and yeast vacuolar (H(+))-ATPases.
The vacuolar (H(+))-ATPases (or V-ATPases) are ATP-dependent proton pumps that function to acidify intracellular compartments in eukaryotic cells. This acidification is essential for such processes as receptor-mediated endocytosis, intracellular targeting of lysosomal enzymes, protein processing and degradation and the coupled transport of small molecules. V-ATPases in the plasma membrane of specialized cells also function in such processes as renal acidification, bone resorption and pH homeostasis. Work from our laboratory has focused on the V-ATPases from clathrin-coated vesicles and yeast vacuoles.Structurally, the V-ATPases are composed of two domains: a peripheral complex (V(1)) composed of eight different subunits (A-H) that is responsible for ATP hydrolysis and an integral complex (V(0)) composed of five different subunits (a, d, c, c' and c") that is responsible for proton translocation. Electron microscopy has revealed the presence of multiple stalks connecting the V(1) and V(0) domains, and crosslinking has been used to address the arrangement of subunits in the complex. Site-directed mutagenesis has been employed to identify residues involved in ATP hydrolysis and proton translocation and to study the topology of the 100 kDa a subunit. This subunit has been shown to control intracellular targeting of the V-ATPase and to influence reversible dissociation and coupling of proton transport and ATP hydrolysis.
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Yoichiro
Y
Arata
Tsuyoshi
T
Nishi
Shoko
S
Kawasaki-Nishi
Elim
E
Shao
Stephan
S
Wilkens
Michael
M
Forgac
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000201:enzymology*; D008958:Models, Molecular; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000201:enzymology*
D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases