| 3.A.2 The H +- or Na+-translocating F-type, V-type and A-type ATPase (F-ATPase) Superfamily
F-type ATPases are found in eukaryotic mitochondria and chloroplasts as well as in bacteria. V-type ATPases are found in vacuoles of eukaryotes and in bacteria. A-type ATPases are found in archaea. All such systems are multisubunit complexes with at least 3 dissimilar subunits embedded as a complex in the membrane (F0, a:b:c = 1:2:~12) and (usually) at least 5 dissimilar subunits attached to F0 (F1,
α:β:γ:δ:&epsilon = 3:3:1:1:1 for F-type ATPases). The eukaryotic proteins are more complicated than the bacterial enzyme complexes. The α, β, δ and F1 hexamer (α3β3) comprise the stator. The rotor (which consists of the c, ε and γ subunits) is believed to rotate relative to the stator in response to either ATP hydrolysis by F1 or proton transport through F0. H+ transport and ATP synthesis may therefore be coupled mechanically. The F1 portion of the bovine mitochondrial F-type ATPase has been solved to 2.8 Ċ resolution.
All eukaryotic F-type ATPases pump 3-4 H+ out of mitochondria, or into thylakoids of chloroplasts, per ATP hydrolyzed. Bacterial F-type ATPases pump 3-4 H+ and/or Na+ (depending on the system) out of the cell per ATP hydrolyzed. These enzymes also operate in the opposite direction, synthesizing ATP when protons flow through the "ATP synthase" down the proton electrochemical gradient (the "proton motive force" or pmf). V-type ATPases may pump 2-3 H+ per ATP hydrolyzed, and these enzymes cannot catalyze pmf-driven ATP synthesis. It has been proposed that this difference between F-type and V-type ATPases is due to a "proton slip" that results from an altered structure in the membrane sector of V-type ATPases (Perzov et al., 2001). This probably results from duplication (intragenic and/or intergenic) of the proteolipid (c) subunit.
Phylogenetic clustering of the integral membrane constituents of F-type ATPases generally corresponds to the phylogenies of the organisms of origin, and consequently the systems in different organisms are probably orthologues. The a subunit of F0 (one copy per complex) spans the membrane five or six times. The b subunits (2 copies per complex; heterodimeric in plant chloroplasts and blue green bacteria) span the membrane once; and the c subunits (called DCCD-binding lipoproteins; reportedly 10, 11, 12, or 14 copies per complex depending on the system) span the membrane two times. Some F-type ATPases such as the Na+-translocating ATPase of Acetobacterium woodii probably contains 3 dissimilar but homologous c-subunit proteolipids of 8 and 18 kDa. The V-type ATPase of S. cerevisiae also has 3 dissimilar c-subunits as mentioned in the next paragraph. While c-subunits in the E. coli F-ATPase have 2 TMSs (one acive site asp per subunit and 12 copies per complex), V-type ATPases have 4 TMSs (one active site glu per subunit and 6 copies per complex), and an archaeal A-ATPase has 6 TMSs (2 active site glus per subunit and 4 subunits per complex).
The α, β and c-subunits of F-type ATPases are homologues to the B, A and c- (or K-) subunits of V-type and A-type ATPases, respectively. Other subunits in these protein complexes are probably homologous to each other, but this fact cannot always be demonstrated by statistical analyses of the sequences. Thus, for the A-type ATPase of Methanosarcina mazei, the V-type ATPase of yeast, and the F-type ATPase of E. coli, respectively, the following subunit equivalences have been suggested: A = Vma1 (A) = β; B = Vma2 (B) = α; C = Vma6 (d) = no E. coli F-type ATPase equivalent; Vma8 (D) = γ; Vma4 (E) = δ; F = Vma7 (F) = ε; I = Vphl/stvl = a+b ?, and K = Vma3 (c) = c. Additionally, the yeast v-type ATPase has 3 dissimilar c-subunits: Vma3(c), Vmal1(c') and Vma6(c"), and three subunits, Vma13(H), Vma5(c) and Vma10(G) which are not found in either the A- or F-type ATPases. All of the yeast vacuolar ATPase subunits have an equivalent subunit in the V-type ATPases of clathrin-coated vesicles of higher eukaryotes.
Eukaryotic V-type ATPases acidify Golgi-derived vesicles, clathrin-coated vesicles, synaptic vesicles, liposomes, and plant vacuoles and function in protein trafficking, receptor-mediated endocytosis, neurotransmitter release, pH regulation, waste management, etc. There are 13 subunits, 8 (A-H) in V1 and 5 (a,c,c',c" and d) in V0. The c-subunits are arranged in a ring with the a-subunit on the outside of the ring. The proton channel may be at the a/c interface, and c rotates relative to a when ATP is hydrolyzed and H+ is translocated. Rotation of V-type ATPases has been demonstrated (Imamura et al., 2003). V-type ATPase proteolipids can form symmetrical 6-membered rings as is true for gap junction sheets from Nephrops norvegicus which are formed by a protein identical to the 4 TMS V-ATPase c-subunit. A 14th subunit, Ac45, associated with V0, is found in some mammalian tissues.
The V-ATPase ring contains three different subunits, c, c' and c" and is therefore probably asymmetric if two or all three are present. By angular reconstitution from electron microscopic images, a 21 Ċ resolution structure shows an asymmetric protein ring with two small openings on the lumenal side and one large opening on the cytoplasmic side. The central hole on the lumenal side is covered by a globular protein while the cytoplasmic opening is covered by two elongated proteins (Wilkens and Forgac, 2001).
The generalized transport reaction for F-type, V-type and A-type ATPases is:
nH+ (in) [or nNa+ (in)] + ATP  nH+ (out) [or nNa+ (out)] + ADP + Pi.
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| References: |
Abrahams, J.P., A.G.W. Leslie, R. Lutter, and J.E. Walker. (1994). Structure at 2.8 Ċ resolution of F1-ATPase from bovine heart mitochondria. Nature 370: 621-628.
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Anraku, Y. (1996). Structure and function of the yeast vacuolar membrane H+-ATPase. In: Handbook of Biological Physics, vol. 2, W.N. Konings, H.R. Daback and J.S. Lolkema (Eds.), Elsevier Science B.V., pp. 93-109.
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Blair, A., L. Ngo, J. Park, I.T. Paulsen, and M.H. Saier, Jr. (1996). Phylogenetic analyses of the homologous transmembrane channel-forming proteins of the F0F1-ATPases of bacteria, chloroplasts and mitochondria. Microbiology 142: 17-32.
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Deckers-Hebestreit, G. and K. Altendorf. (1996). The F0F1-type ATP synthases of bacteria: structure and function of the F0 complex. Ann. Rev. Microbiol. 50: 791-824.
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Dimroth, P., H. Wang, M. Grabe, and G. Oster. (1999). Energy transduction in the sodium F-ATPase of Propionigenium modestum. Proc. Natl. Acad. Sci. USA 96: 4924-4929.
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Elston, T., H. Wang, and G. Oster. (1998). Energy transduction in ATP synthase. Nature 391: 510-513.
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Forgac, M. (1999). Structure and properties of the vacuolar (H+)-ATPases. J. Biol. Chem. 274: 12951-12954.
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Goldsmith, E.J. (1996). Allosteric enzymes as models for chemomechanical energy transducing assemblies. FASEB J. 10: 702-708.
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Harrison, M.A., J. Murray, B. Powell, Y.-I. Kim, M.E. Finbow, and J.B.C. Findlay. (1999). Helical interactions and membrane disposition of the 16-kDa proteolipid subunit of the vacuolar H+-ATPase analyzed by cysteine replacement mutagenesis. J. Biol. Chem. 274: 25461-25470.
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Hilario, E. and J.P. Gogarten. (1998). The prokaryote-to-eukaryote transition reflected in the evolution of the V/F/A-ATPase catalytic and proteolipid subunits. J. Mol. Evol. 46: 703-715.
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Imamura, H., M. Nakano, H. Noji, E. Muneyuji, S. Ohkuma, M. Yoshida, and K. Yokoyama. (2003). Evidence for rotation of V1-ATPase. Proc. Natl. Acad. Sci. USA 100: 2312-2315.
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Jones, P.C., W. Jiang, and R.H. Fillingame. (1998). Arrangement of the multicopy H+-translocating subunit c in the membrane sector of the Escherichia coli F1F0 ATP synthase. J. Biol. Chem. 273: 17178-17185.
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Kakinuma, Y., I. Yamato, and T. Murata. (1999). Structure and function of vacuolar Na+-translocating ATPase in Enterococcus hirae. J. Bioenerg. Biomemb. 31: 7-14.
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Kane, P.M. (1999). Vacuolar ATPases: structure, function, assembly and biosynthesis. J. Bioenerg. Biomembr. 31: 1-83.
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Kinosita, K., Jr., R. Yasuda, H. Noji, S. Ishiwata, and M. Yoshida. (1998). F1-ATPase: a rotory motor made of a single molecule. Cell 93: 21-24.
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Long, J.C., S. Wang, and S.B. Vik. (1998). Membrane topology of subunit a of the F1F0 ATP synthase as determined by labeling of unique cysteine residues. J. Biol. Chem. 273: 16235-16240.
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Müller, V., C. Ruppert, and T. Lemker. (1999). Structure and function of the A1A0-ATPases from methanogenic archaea. J. Bioenerg. 31: 15-27.
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Nakamoto, R.K. (1996). Mechanisms of active transport in the F0F1 ATP synthase. J. Membr. Biol. 151: 101-111.
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Nelson, N. and W.R. Harvey. (1999). Vacuolar and plasma membrane proton-adenosinetriphosphatases. Physiol. Rev. 79: 361-385.
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Noji, H., R. Yasuda, M. Yoshida, and K. Kinosita, Jr. (1997). Direct observation of the rotation of F1-ATPase. Nature 386: 299-302.
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Perzov, N., V. Padler-Karavani, H. Nelson, and N. Nelson. (2001). Features of V-ATPases that distinguish them from F-ATPases. FEBS Lett. 504: 223-228.
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Rahlfs, S. and V. Müller. (1997). Sequence of subunit c of the Na+-translocating F1F0 ATPase of Acetobacterium woodii: proposal for determinants of Na+ specificity as revealed by sequence comparisions. FEBS Lett. 404: 269-271.
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Rahlfs, S., S. Aufurth, and V. Müller. (1999). The Na+-F1F0-ATPase operon from Acetobacterium woodii operon structure and presence of multiole copies of atpE which encode proteolipids of 8- and 18-kDa. J. Biol. Chem. 274: 33999-34004.
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Rastogi, V.K. and M.E. Girvin. (1999). Structural changes linked to protein translocation by subunit C of the ATP synthase. Nature 402: 263-268.
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Ruppert, C., H. Kavermann, S. Wimmers, R. Schmid, J. Kellermann, F. Lottspeich, H. Huber, K.O. Stetter, and V. Müller. (1999). The proteolipid of the A1A0 ATP synthase from Methanococcus jannaschii has six predicted transmembrane helices but only two proton-translocating carboxyl groups. J. Biol. Chem. 274: 25281-25284.
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Sambongi, Y., Y. Iko, M. Tanabe, H. Omote, A. Iwamoto-Kihara, I. Ueda, T. Yanagida, Y. Wada, and M. Futai. (1999). Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Science 286: 1722-1723.
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Schulenberg, B., R. Aggeler, J. Murray, and R.A. Capaldi. (1999). The ge-c subunit interface in the ATP synthase of Escherichia coli cross-linking of the e subunits to the c subunit ring does not impair enzyme function, that of g to c subunits leads to uncoupling. J. Biol. Chem. 274: 34233-34237.
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Solioz, M. and K. Davies. (1994). Operon of vacuolar-type Na+-ATPase of Enterococcus hirae. J. Biol. Chem. 269: 9453-9459.
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Wilkens, S. and M. Forgac (2001). Three-dimensional structure of the vacuolar ATPase proton channel by electron microscopy. J. Biol. Chem. 276: 44064-44068.
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Xu, T. and M. Forgac. (2000). Subunit D (Vma8p) of the yeast vacuolar H+-ATPase plays a role in coupling of proton transport and ATP hydrolysis. J. Biol. Chem. 275: 22075-22081.
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Yamada, H., Y. Moriyama, M. Maeda, and M. Futai. (1996). Transmembrane topology of Escherichia coli H+-ATPase (ATP synthase) subunit a. FEBS Lett. 390: 34-38.
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Yokoyama, K., S. Ohkuma, H. Taguchi, T. Yasunaga, T. Wakabayashi, and M. Yoshida. (2000). V-Type H+-ATPase/synthase from a thermophilic eubacterium, Thermus thermophilus. J. Biol. Chem. 275: 13955-13961.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 3.A.2.1.1 | H+-translocating F-type ATPase | Bacteria; eukaryotic mitochondria and chloroplast | F-type ATPase of E. coli |
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| 3.A.2.1.2 | Na+-translocating F-type ATPase | Bacteria | F-type ATPase of Propionigenium modestum |
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| 3.A.2.1.3 | H+-translocating F-type ATPase | Yeast | F-type ATPase of Saccharomyces cerevisiae ATP6; ATP8; ATP9; ATP1; ATP3; ATP16; ATP5; ATP2; ATP7; ATP14; ATP4; ATP15 |
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| 3.A.2.2.1 | H+-translocating V-type ATPase | Bacteria; eukaryotes | V-type ATPase of Thermus thermophilus |
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| 3.A.2.2.2 | Na+-translocating V-type ATPase | Bacteria | V-type ATPase of Enterococcus hirae NtpLMNOPQ |
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| 3.A.2.2.3 | H+-translocating V-type ATPase | Eukaryotes | V-type ATPase of Saccharomyces cerevisiae VMA2; VMA1; CUP5; VMA8; VMA7; PPA1; VMA10; VMA5; VMA6; VPH1; YMA4; VMA11; VMA13 |
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| 3.A.2.3.1 | H+-translocating A-type ATPase | Archaea | A-type ATPase of Methanosarcina mazei AhaABCDEFG |
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