Requirement of the hinge domain for dimerization of Ca2+-ATPase large cytoplasmic portion expressed in bacteria

Carvalho-Alves, P C; Hering, Vitor Renaux; Oliveira, Juliana Michelli S.; Salinas, Roberto Köpke; Verjovski-Almeida, Sérgio

doi:10.1016/s0005-2736(00)00206-6

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…Dimerization is sometimes considered as an activation mechanism [27]. Homodimer formation of the Ca 2+ -ATPase involves the N-terminal ends and the large cytoplasmic loop [28,29]. In the yeast and plant H + -ATPases, the native enzyme exists as a homodimer of catalytic subunits [4,9,13,30].…”

Section: The Regulatory Domainmentioning

confidence: 99%

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

Duby

Boutry

2008

Pflugers Arch - Eur J Physiol

198

126

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Around 40 P-type ATPases have been identified in Arabidopsis and rice, for which the genomes are known. None seems to exchange sodium and potassium, as does the animal Na(+)/K(+)-ATPase. Instead, plants, together with fungi, possess a proton pumping ATPase (H(+)-ATPase), which couples ATP hydrolysis to proton transport out of the cell, and so establishes an electrochemical gradient across the plasma membrane, which is dissipated by secondary transporters using protons in symport or antiport, as sodium is used in animal cells. Additional functions, such as stomata opening, cell growth, and intracellular pH homeostasis, have been proposed. Crystallographic data and homology modeling suggest that the H(+)-ATPase has a broadly similar structure to the other P-type ATPases but has an extended C-terminal region, which is involved in enzyme regulation. Phosphorylation of the penultimate residue, a Thr, and the subsequent binding of regulatory 14-3-3 proteins result in the formation of a dodecamer (six H(+)-ATPase and six 14-3-3 molecules) and enzyme activation. This type of regulation is unique to the P-type ATPase family. However, the recent identification of additional phosphorylated residues suggests further regulatory features.

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Section: The Regulatory Domainmentioning

confidence: 99%

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

Duby

Boutry

2008

Pflugers Arch - Eur J Physiol

198

126

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“…Thus, the titration of Ca 2ϩ -ATPase and Ca 2ϩ uptake activities with fluorescein isothiocyanate (16), radiation inactivation analysis of pump activity and integrity (17,18), freeze-fracture and deep-etching of sarcoplasmic reticular membranes (19,20), and analysis with photoaffinity spin-labeled derivative of ATP (21) all suggested that the functional unit of the Ca 2ϩ -ATPase is a dimer. Furthermore, an analysis of a purified 48-kDa SERCA1 fusion protein by small angle x-ray scattering suggested a requirement of the hinge domain (amino acids 670 -728) region for self-association of the large hydrophilic domain into a dimer (22). Thus, it is possible that the mutant pumps affect the WT pump by way of protein interaction.…”

Section: Protein Levels Of Serca2bmentioning

confidence: 99%

Multiple Effects of SERCA2b Mutations Associated with Darier's Disease

Ahn

Lee

Kim

et al. 2003

Journal of Biological Chemistry

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Darier's disease (DD) is an autosomal dominant disorder caused by mutations in the ATP2A2 gene, encoding sarco/endoplasmic reticulum Ca 2؉ -ATPase pump type 2b isoform (SERCA2b). Although >100 mutations in the ATP2A2 gene were identified, no apparent relation between genotype/phenotype emerged. In this work, we analyzed 12 DD-associated mutations from all of the regions of SERCA2b to study the underlying pathologic mechanism of DD and to elucidate the role of dimerization in SERCA2b activity. Most mutations markedly affected protein expression, partially because of enhanced proteasome-mediated degradation. All of the mutants showed lower activity than the wild type pump. Notably, several mutants that cause relatively severe phenotype of DD inhibited the activity of the endogenous and the co-expressed wild type SERCA2b. Importantly, these effects were not attributed to changes in passive Ca 2؉ leak, inositol 1,4,5-trisphosphate receptor activity, or sensitivity to inositol 1,4,5-trisphosphate. Rather, co-immunoprecipitation experiments showed that SERCA2b monomers interact to influence the activity of each other. These findings reveal multiple molecular mechanisms to account for the plethora of pathologic states observed in DD and provide the first evidence for the importance of SERCA2b dimerization in pump function in vivo.Darier's disease (DD, 1 OMIM 124200), also known as keratosis follicularis, is an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization (1). DD is also associated with an increased prevalence of neuropsychiatric disorders including bipolar disorders, schizophrenia, epilepsy, and mental retardation (1). Recently, mutations in the ATP2A2 gene encoding the sarco/endoplasmic reticulum Ca 2ϩ -ATPase pump type 2b isoform (SERCA2b) have been identified as a cause of DD (2). SERCA2b is a housekeeping protein, which is expressed ubiquitously and is responsible for Ca 2ϩ uptake into the ER, including the agonist-mobilizable Ca 2ϩ pool (3, 4). By determining ER Ca 2ϩ load, the SERCA2 pumps modulate several parameters of the Ca 2ϩ signal. In resting cells, the SERCA2 pump provides the bulk of the dynamic Ca 2ϩ -buffering capacity to prevent large fluctuation in [Ca 2ϩ ] i (5). In stimulated cells, SERCA2 controls the activity of the store-operated Ca 2ϩ influx channel by preventing accumulation of Ca 2ϩ at the mouth of the channels and their inhibition by [Ca 2ϩ ] i (6). SERCA2b reloads the ER with Ca 2ϩ at the end of cell stimulation (5) and between Ca 2ϩ spikes to determine the frequency of Ca 2ϩ oscillations (7), and to control the diverse cellular functions regulated by [Ca 2ϩ ] i and Ca 2ϩ oscillations (8, 9). Alteration in SERCA2 pump function by overexpression in Chinese hamster ovary cells (10) or partial deletion in mice (7) lead to adaptation of the Ca 2ϩ signaling machinery and Ca 2ϩ -regulated cell functions that translates to nearly normal physiological response in the majority of organs and tissues. This co...

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“…[31] suggested a monomer–dimer transition model of Ca 2+ ‐ATPase, in which the cytoplasmic domains clap like a castanet duet, and Carvalho‐Alves et al . [32] proposed dimerization of the cytoplasmic domain of Ca 2+ ‐ATPase. Abe et al .…”

Section: Discussionmentioning

confidence: 99%

“…This state may loosely associate with another E state at the cytoplasmic domain, as shown by Carvalho‐Alves et al . [32]. E2( i )P, which corresponds to K + ‐insensitive E 2 P, is drawn as a compact form.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of p‐nitrophenylphosphatase activity of Na⁺/K⁺‐ATPase by NaCl with oligomycin or ATP

Homareda¹,

Ushimaru²

2005

The FEBS Journal

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It is known that the addition of NaCl with oligomycin or ATP stimulates ouabain‐sensitive and K+‐dependent p‐nitrophenylphosphatase (pNPPase) activity of Na+/K+‐ATPase. We investigated the mechanism of the stimulation. The combination of oligomycin and NaCl increased the affinity of pNPPase activity for K+. When the ratio of Na+ to Rb+ was 10 in the presence of oligomycin, Rb+‐binding and pNPPase activity reached a maximal level and Na+ was occluded. Phosphorylation of Na+/K+‐ATPase by p‐nitrophenylphosphate (pNPP) was not affected by oligomycin. Because oligomycin stabilizes the Na+‐occluded E1 state of Na+/K+‐ATPase, it seemed that the Na+‐occluded E1 state increased the affinity of the phosphoenzyme formed from pNPP for K+. On the other hand, the combination of ATP and NaCl also increased the affinity of pNPPase for K+ and activated ATPase activity. Both activities were affected by the ligand conditions. Oligomycin noncompetitively affected the activation of pNPPase by NaCl and ATP. Nonhydrolyzable ATP analogues could not substitute for ATP. As NaE1P, which is the high‐energy phosphoenzyme formed from ATP with Na+, is also the Na+‐occluded E1 state, it is suggested that the Na+‐occluded E1 state increases the affinity of the phosphoenzyme from pNPP for K+ through the interaction between α subunits. Therefore, membrane‐bound Na+/K+‐ATPase would function as at least an (αβ)2‐diprotomer with interacting α subunits at the phosphorylation step.

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Requirement of the hinge domain for dimerization of Ca2+-ATPase large cytoplasmic portion expressed in bacteria

Cited by 10 publications

References 38 publications

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

Multiple Effects of SERCA2b Mutations Associated with Darier's Disease

Stimulation of p‐nitrophenylphosphatase activity of Na⁺/K⁺‐ATPase by NaCl with oligomycin or ATP

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Requirement of the hinge domain for dimerization of Ca2+-ATPase large cytoplasmic portion expressed in bacteria

Cited by 10 publications

References 38 publications

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles

Multiple Effects of SERCA2b Mutations Associated with Darier's Disease

Stimulation of p‐nitrophenylphosphatase activity of Na+/K+‐ATPase by NaCl with oligomycin or ATP

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Stimulation of p‐nitrophenylphosphatase activity of Na⁺/K⁺‐ATPase by NaCl with oligomycin or ATP