V-ATPase

Seidel, T., Golldack, D. and Dietz, K. J. (2005). Mapping of C-termini of V-ATPase subunits by in vivo-FRET measurements. FEBS Lett. 579, 4374-82. 

The V-ATPase pumps protons into Golgi-derived organelles 82... 

Vasilyeva, E., Forgac, M., Interaction of the clathrin-coated vesicle V-ATPase with ADP and sodium azide. J Biol Chem 273, 23823-23829 (1988). 

Scimeca, J.G., Franchi, A., Trojani, C., Parrinello, H., Grosgeorge, J., Robert, C., Jaillon, O., Poirier, C., Gaudray, P., and Carle, G.F. (2000) The Gene Encoding the Mouse Homologue of the Specific 116 kDa V ATPase Subunit Bears a Deletion in Osteosclerotic (oc/oc) Mutants. Bone26, 207-13. 

This strategy has already been found useful in natural product synthesis. In the course of a synthesis of V-ATPase inhibitor oximidine HI, John Porco of Boston University has described (Angew. Chem. Ini. Ed. 2004,43, 3601) the cyclization of 7 to 8. In the absence of the pententyl director, the initial complexation of the Ru catalyst was with the 1,3-diene, leading to allylidene complex and so effectively killing the catalyst. In this case, the Hoveyda catalyst 8 provided a cleaner product than G2 did. 

Two other types of proton-pumping ATPases are considered in Chapter 18. One is the mitochondrial F,F0 ATPase, which ordinarily operates in the reverse direction as the body s principal ATP synthase. The other type, which in some ways resembles the mitochondrial FjFq ATPase, is the vacuolar ATPase (V-ATPase). These are true proton pumps which acidify vacuoles of plants and also lysosomes and phagocytic vacuoles.554 555 They are also considered in Chapter 18. 

This would extend our model of balanced HC1 transport for mineral dissolution, but additional studies are required to understand the integration of this model (Blair et al., 2002), Figure 2. There is a pervasive cytoskeletal-src dependence of proper targeting for the ion transporters of osteoclasts (Zuo et al., 2006 Tehrani et al., 2006 Abu-Amer et al., 1997 Soriano et al., 1991). The actin-directed disposition of CLIC protein has also been observed in microvilli of placental cells (Berryman et al., 2004). In osteoclasts the coordinated disposition of V-ATPase and CLIC required for full expression of the bone resorption phenotype (Edwards et al., 2006). It is clear that much of the osteoclasts organization exists to support the massive acid secretion for bone calcium solubilization. 

A unique feature of the F/V/A-ATPases is that they are rotary molecular motor enzymes. This has been shown by experiment for members of the F-and V-ATPase subfamilies and is generally assumed to be true for the closely related A-ATPases as well. The two enzymatic processes, ATP synthesis/hydrolysis and ion translocation, are coupled via a rotational motion of a central domain of the complex (the rotor) relative to a static domain (the stator). The A-, F-, and V-ATPases represent the smallest rotary motors found in the living cell so far. Most of what we know about the structure and mechanism of these microscopic energy converters comes from studies conducted with the F-ATPase. In the following review, current structural knowledge for all three members of the family of F-, V-,... 

V-ATPase A-ATPasea Thermoplasma acidophilum F-ATPase Escherichia coli... 

The subunit nomenclature for the A-ATPase is Kfor the proteolipid, I for the V- and F-ATPase a-subunit, and C for the V-ATPase subunit d. The small polypeptide called H in the A-ATPase is probably the homologue of the V-ATPase G-subunit. 

In the cell, the vacuolar ATPase functions exclusively as an ATP hydrolysis-driven proton pump. This functional preference of the vacuolar ATPase seems not to be due to a fundamental structural difference compared with the ATP synthase because it has been shown that the V-ATPase can be reversed to synthesize ATP in vitro, albeit with very low efficiency (Hirata et al., 2000). 

F- and V-ATPase are evolutionarily related (Gogarten et al., 1989 Nelson and Taiz, 1989). This relationship between F- and V-ATPases was first described based on the similarity of the amino acid sequence of the V-ATPase A- and B-subunits and the F-ATPase jS- and a-subunits,... 

Enzymes that are structurally related to the eukaryotic V-ATPase are also found in certain eubacteria (Speelmans etal., 1994 Takase etal., 1994 Yokoyama etal., 1990). Based on nucleotide sequence analysis, it is believed that these bacterial V-like ATPases have been introduced into the eubacteria via horizontal gene transfer from Archaea (Hilario and Gogarten, 1993, 1998). The subunit composition of the bacterial V-like ATPase is indeed more similar to the archaeal A-ATPase than to the eukaryotic V-ATPase, and we will therefore treat the bacterial V-ATPase—like enzyme together with the archaeal A-ATPase (see below). In the following, we will use the name V-ATPase only for the eukaryotic enzyme, and we will call the bacterial enzyme the A/V-type ATPase as suggested by Hilario and Gogarten (1998). 

Besides its function as a proton pump, the V-ATPase has been shown to interact with a variety of other cellular protein components such as ectoapyrase (Zhang et al, 2000), the yeast RAVE complex (Smardon et al, 2002), and HIV Nef and AP-2 (Geyer et al, 2002 Lu et al, 1998). 

The Vo is made of subunits acc c"de. Subunits c, c, and c" are proteolipid isoforms each containing one essential lipid-exposed glutamate residue. The proteolipids in the V-ATPase are twice the size compared with the F-ATPase proteolipids, and it is assumed that the four transmembrane a helix c- and c -subunits are a result of an early gene fusion event. Subunit c" has two lipid-exposed glutamates, but only one of them is essential for proton pumping. The 100-kDa subunit a is a two-domain protein with a... 

Based on sequence comparison, the eubacterial V-type ATPase is a product of horizontal gene transfer from the Archaea. Much of the information about the subunit arrangement in the eubacterial A/V-type—like ATPase comes from studies with the enzymes from C. fervidus and T. thermophilus (Boekema et al, 1997, 1999 Ubbink-Kok et al, 2000 Yokoyama et al, 2003a). A recent 3D reconstruction of the A/V- ATPase from T. thermophilus (Bernal and Stock, 2004) revealed the structural similarity to both the eukaryotic V-ATPase (Domgall et al., 2002 Wilkens et al., 2004, 2005) and the archaeal A-ATPase (Coskun et al., 2004a,b). The x-ray crystal structure for the C-subunit of the bacterial A/V-like ATPase has been reported recently (Iwata et al, 2004). The C-subunit of the bacterial V-like ATPase shows limited but significant sequence homology to the cZ-subunit of the eukaryotic V-ATPase. 

In the V-ATPase, the presence of at least two peripheral stators has been reported (Boekema et al., 1999 Domgall et al., 2002 Wilkens et al., 1999, 2004). Candidates for the stator proteins in the V-ATPase are subunits E and G, and support for this assignment comes from photochemical cross-linking studies that place these subunits on the outside of the Vi domain for much of its length (Arata et al., 2002a,b). Another subunit that probably plays the role of a stator in the V-ATPase is the a-subunit of the Vo- The Vo a-subunit has a large cytoplasmic domain, and it has been shown that this domain interacts with the A-subunit of the Vi (Landolt-Marticorena et al, 2000). 

Arata, Y., Baleja, J. D., and Forgac, M. (2002a). Localization of subunits D, E, and G in the yeast V-ATPAse complex using cysteine mediated cross-linking to subunit B. Biochemistry 41, 11301-11307. 

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