The little we know on the structure and machinery of V-ATPase

Saroussi, Shai; Nelson, Nathan

doi:10.1242/jeb.025866

Cited by 49 publications

(35 citation statements)

References 58 publications

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“…Although there is no structure available for the eukaryotic EG heterodimer, the proteins comprising the peripheral stalk (EH) 4 in the related archaeal A-and bacterial A/VATPase are more stable and thus have been more amenable to structural characterization than their eukaryotic counterparts. Although the archaeal EG heterodimer is shorter in length and more stable than yeast EG, their secondary structure predictions and biological functions are similar (50,51), indicating that they may be used as a structural model for eukaryotic EG.…”

Section: Discussionmentioning

confidence: 99%

“…In all eukaryotic cells, V-ATPase function sets up an electrochemical potential and acidifies intracellular compartments (1)(2)(3)(4)(5). These functions make the V-ATPase a crucial enzyme involved in intracellular traffic, vesicular transport, endo/exocytosis, and pH homeostasis.…”

mentioning

confidence: 99%

“…These two lobes are composed of distinct functional domains, a soluble catalytic sector, V 1 , and a membrane integral proton pore, V o . The V 1 sector contains subunits A 3 B 3 (C)DE 3 FG 3 H, and the V o is made of ac [3][4] cЈcЉde. Most V-ATPase subunits have functional and structural counterparts in the A-and F-type motors; however, only the nucleotide-binding and proteolipid subunits share significant sequence identity.…”

mentioning

confidence: 99%

“…Much like in the F-ATP synthase, the AB subunits come together in an alternating arrangement to form a catalytic hexamer with nucleotide-binding sites located at the AB interfaces (14,15). ATP hydrolysis-driven rotation of a central rotor domain, composed of subunits DFd and a ring of the proteolipid subunits, c [3][4] cЈcЉ, is coupled to proton translocation along the interface of the proteolipid ring and the C-terminal domain of the a subunit. During catalysis, three peripheral stalks (each formed by a subunit EG heterodimer) in conjunction with subunits C and H and the N-terminal domain of subunit a (a NT ), resist the torque of rotation, thus keeping the A 3 B 3 hexamer static and allowing for rotation to be productive.…”

mentioning

confidence: 99%

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Domain Characterization and Interaction of the Yeast Vacuolar ATPase Subunit C with the Peripheral Stator Stalk Subunits E and G

Oot

Wilkens

2010

Journal of Biological Chemistry

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To determine which subunit C domain binds EG with high affinity, we have generated C head and C foot and characterized their interaction with subunit EG heterodimer. Our findings indicate that the high affinity site for EGC interaction is C head . In addition, we provide evidence that the EGC head interaction greatly stabilizes EG heterodimer.2 is a ubiquitous multisubunit enzyme that couples the free energy of ATP hydrolysis to active proton transport. In all eukaryotic cells, V-ATPase function sets up an electrochemical potential and acidifies intracellular compartments (1-5). These functions make the V-ATPase a crucial enzyme involved in intracellular traffic, vesicular transport, endo/exocytosis, and pH homeostasis. In the specialized cells of higher eukaryotes, plasma membrane-associated V-ATPases serve to acidify the extracellular space. The malfunction of the V-ATPase in these cells has been linked to a range of diseases including osteoporosis, diabetes, renal tubular acidosis, and cancer (6 -9). As shown in EM images and reconstructions, the V-ATPase is bilobular in overall structure, typical of the rotary ATPases (10 -13). These two lobes are composed of distinct functional domains, a soluble catalytic sector, V 1 , and a membrane integral proton pore, V o . The V 1 sector contains subunits A 3 B 3 (C)DE 3 FG 3 H, and the V o is made of ac 3-4 cЈcЉde. Most V-ATPase subunits have functional and structural counterparts in the A-and F-type motors; however, only the nucleotide-binding and proteolipid subunits share significant sequence identity. Much like in the F-ATP synthase, the AB subunits come together in an alternating arrangement to form a catalytic hexamer with nucleotide-binding sites located at the AB interfaces (14, 15). ATP hydrolysis-driven rotation of a central rotor domain, composed of subunits DFd and a ring of the proteolipid subunits, c 3-4 cЈcЉ, is coupled to proton translocation along the interface of the proteolipid ring and the C-terminal domain of the a subunit. During catalysis, three peripheral stalks (each formed by a subunit EG heterodimer) in conjunction with subunits C and H and the N-terminal domain of subunit a (a NT ), resist the torque of rotation, thus keeping the A 3 B 3 hexamer static and allowing for rotation to be productive.Unlike F-ATPase, the activity of eukaryotic V-ATPase is regulated by a unique mechanism of reversible dissociation, a process first described for the enzymes from yeast and insect (16, 17) but more recently also found in cells of higher animals (18 -20). In yeast under conditions of nutrient deprivation, the V 1 sector dissociates from the V o sector, and both are functionally silenced (21,22). Although dissociated, a single V 1 subunit, C, is released into the cytosol and is reincorporated into the enzyme upon nutrient readdition (16). Because the C subunit has been proposed to be a molecular switch for controlled enzyme dissociation, the interactions between the C subunit and its intraenzyme binding partners are of particular interest.The crystal ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Domain Characterization and Interaction of the Yeast Vacuolar ATPase Subunit C with the Peripheral Stator Stalk Subunits E and G

Oot

Wilkens

2010

Journal of Biological Chemistry

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“…The V-ATPase is composed of several subunits, which are assembled into two distinct V 0 and V 1 domains. The structure of this complex enzyme is described in detail in other reviews elsewhere in this issue (Saroussi and Nelson, 2009;Wieczorek et al, 2009). In mammals, the V 0 domain contains five transmembrane subunits (a, d, e, c and cЉ) and the V 1 domain contains eight cytosolic subunits (A to H) (see also Beyenbach and Wieczorek, 2006;Forgac, 2007;Wagner et al, 2004).…”

Section: Clear Cells Express the V-atpase In Their Apical Membranementioning

confidence: 99%

Regulation of luminal acidification in the male reproductive tract via cell–cell crosstalk

Shum

Silva

Brown

et al. 2009

Journal of Experimental Biology

123

101

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Ion Transport across Nonexcitable Membranes

Reuss

2011

Encyclopedia of Life Sciences

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Membrane transport proteins can perform either active or passive ion transport. Active transport, in the absence or against the prevailing electrochemical gradient, can be either primary (ion pumps such as ATPases) or secondary (carriers performing cotransport or exchange). Passive transport of ions, down the electrochemical gradient, is largely mediated by ion channels. In a cell in the steady state, plasma‐membrane active and passive transport processes result in equal and opposite ion fluxes. The ion gradients generate an electrical potential difference (membrane voltage) across the cell membrane because the latter exhibits selective ionic permeability. The resting membrane potential in most cells is largely determined by the K + equilibrium potential, with the cell being negative to the extracellular solution. Ion channels participate in numerous cell functions and their mutations can result in diseases whose manifestations depend on the organs and systems in which these proteins are expressed. Key Concepts: The difference in composition between intracellular and extracellular fluids depends on the barrier and transport functions of the plasma membrane. Transport across the plasma membrane can be by solubility‐diffusion (via the lipid bilayer) or mediated (via membrane proteins). Ion transport is mediated via membrane proteins (channels, carriers or pumps). The differences in ion concentrations across the plasma membrane determine the membrane potential difference (membrane voltage), according to the magnitude of the concentration gradients and the ion permeability. Active transport is thermodynamically uphill (in the absence of or against the electrochemical gradient). It can be primary (pumps), for example, driven by ATP hydrolysis, or secondary (carriers), driven by the electrochemical gradient for one of the substrates. Passive transport can occur by solubility‐diffusion via the lipid bilayer or be mediated by carriers or channels. In the case of ions passive transport is largely via channels. The ion current through channels of one kind depends on the number of channels per cell or unit surface area, their open probability, their conductance and the electrochemical driving force. Ion channels are classified by their selectivity to ions. The most important ion channels expressed on the plasma membrane of nonexcitable cells are selective for K + , Na + , Ca 2+ , H + , Cl − , cations or anions. Numerous genetic diseases of ion channels have been identified. They involve gain‐ or loss‐of‐function mutations that alter the function of one or more organs.

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The little we know on the structure and machinery of V-ATPase

Cited by 49 publications

References 58 publications

Domain Characterization and Interaction of the Yeast Vacuolar ATPase Subunit C with the Peripheral Stator Stalk Subunits E and G

Domain Characterization and Interaction of the Yeast Vacuolar ATPase Subunit C with the Peripheral Stator Stalk Subunits E and G

Regulation of luminal acidification in the male reproductive tract via cell–cell crosstalk

Ion Transport across Nonexcitable Membranes

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