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J Biol Chem
2012 May 04;28719:15959-65. doi: 10.1074/jbc.M112.340406.
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Protein kinase A (PKA) phosphorylation of Na+/K+-ATPase opens intracellular C-terminal water pathway leading to third Na+-binding site in molecular dynamics simulations.
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Phosphorylation is one of the major mechanisms for posttranscriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all-atom Molecular Dynamics simulations to investigate the structural consequences of phosphorylating the Na(+)/K(+)-ATPase (NKA) residue Ser(936), which is the best characterized phosphorylation site in NKA, targeted in vivo by protein kinase A (PKA). The Molecular Dynamics simulations suggest that Ser(936) phosphorylation opens a C-terminal hydrated pathway leading to Asp(926), a transmembrane residue proposed to form part of the third sodium ion-binding site. Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic the effects of Ser(936) phosphorylation. The results establish a structural association of Ser(936) with the C terminus of NKA and indicate that phosphorylation of Ser(936) can modulate pumping activity by changing the accessibility to the ion-binding site.
Andersson,
Forskolin-induced down-regulation of Na+,K(+)-ATPase activity is not associated with internalization of the enzyme.
1998, Pubmed
Andersson,
Forskolin-induced down-regulation of Na+,K(+)-ATPase activity is not associated with internalization of the enzyme.
1998,
Pubmed Awayda,
Protein kinase regulation of a cloned epithelial Na+ channel.
1996,
Pubmed
,
Xenbase Berger,
Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature.
1997,
Pubmed Bertorello,
Phosphorylation of the catalytic subunit of Na+,K(+)-ATPase inhibits the activity of the enzyme.
1991,
Pubmed Blanco,
Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function.
1998,
Pubmed Chakrabarti,
An iris-like mechanism of pore dilation in the CorA magnesium transport system.
2010,
Pubmed Cheng,
[Ca2+]i determines the effects of protein kinases A and C on activity of rat renal Na+,K+-ATPase.
1999,
Pubmed Cheng,
PKA-mediated phosphorylation and inhibition of Na(+)-K(+)-ATPase in response to beta-adrenergic hormone.
1997,
Pubmed Chibalin,
Phosphorylation of Na,K-ATPase alpha-subunits in microsomes and in homogenates of Xenopus oocytes resulting from the stimulation of protein kinase A and protein kinase C.
1992,
Pubmed
,
Xenbase Codina,
Phosphorylation of S955 at the protein kinase A consensus promotes maturation of the alpha subunit of the colonic H+,K+ -ATPase.
2006,
Pubmed Espinoza-Fonseca,
Atomic-level characterization of the activation mechanism of SERCA by calcium.
2011,
Pubmed Feschenko,
Conformation-dependent phosphorylation of Na,K-ATPase by protein kinase A and protein kinase C.
1994,
Pubmed Groban,
Conformational changes in protein loops and helices induced by post-translational phosphorylation.
2006,
Pubmed Hess,
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.
2008,
Pubmed Hess,
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation.
2008,
Pubmed Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed Kristensen,
Trafficking of Na,K-ATPase fused to enhanced green fluorescent protein is mediated by protein kinase A or C.
2003,
Pubmed Law,
An ion gating mechanism of gastric H,K-ATPase based on molecular dynamics simulations.
2008,
Pubmed Lee,
The cAMP-dependent kinase pathway does not sensitize the cloned vanilloid receptor type 1 expressed in xenopus oocytes or Aplysia neurons.
2000,
Pubmed
,
Xenbase Meier,
Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase {alpha} subunit.
2010,
Pubmed
,
Xenbase Morth,
The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations.
2009,
Pubmed Morth,
A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps.
2011,
Pubmed Morth,
Crystal structure of the sodium-potassium pump.
2007,
Pubmed Musgaard,
Protonation states of important acidic residues in the central Ca²⁺ ion binding sites of the Ca²⁺-ATPase: a molecular modeling study.
2011,
Pubmed Oliveira,
Prostaglandin E2 modulates Na+,K+-ATPase activity in rat hippocampus: implications for neurological diseases.
2009,
Pubmed Piana,
How robust are protein folding simulations with respect to force field parameterization?
2011,
Pubmed Poulsen,
Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase.
2010,
Pubmed
,
Xenbase Poulsen,
Phosphorylation of the Na+,K+-ATPase and the H+,K+-ATPase.
2010,
Pubmed Provasi,
Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics.
2009,
Pubmed Ramachandran,
A structural model of the pore-forming region of the skeletal muscle ryanodine receptor (RyR1).
2009,
Pubmed Shinoda,
Crystal structure of the sodium-potassium pump at 2.4 A resolution.
2009,
Pubmed Stansfeld,
Molecular simulation approaches to membrane proteins.
2011,
Pubmed Tavraz,
Diverse functional consequences of mutations in the Na+/K+-ATPase alpha2-subunit causing familial hemiplegic migraine type 2.
2008,
Pubmed
,
Xenbase Teixeira,
Isoform-specific regulation of Na+,K+-ATPase endocytosis and recruitment to the plasma membrane.
2003,
Pubmed Therien,
Mechanisms of sodium pump regulation.
2000,
Pubmed Tieleman,
Membrane protein simulations with a united-atom lipid and all-atom protein model: lipid-protein interactions, side chain transfer free energies and model proteins.
2006,
Pubmed Toustrup-Jensen,
The C terminus of Na+,K+-ATPase controls Na+ affinity on both sides of the membrane through Arg935.
2009,
Pubmed Van Der Spoel,
GROMACS: fast, flexible, and free.
2005,
Pubmed Venosa,
Protein kinases A and C stimulate the Na+ active transport in frog skeletal muscle without an appreciable change in the number of sarcolemmal Na+ pumps.
2005,
Pubmed Vinciguerra,
Intracellular Na+ controls cell surface expression of Na,K-ATPase via a cAMP-independent PKA pathway in mammalian kidney collecting duct cells.
2003,
Pubmed Wang,
Control of cation permeation through the nicotinic receptor channel.
2008,
Pubmed Witzke,
Inclusion of terpenoid plant extracts in lipid bilayers investigated by molecular dynamics simulations.
2010,
Pubmed Wu,
Involvement of dopamine system in regulation of Na+,K+-ATPase in the striatum upon activation of opioid receptors by morphine.
2007,
Pubmed Yaragatupalli,
Altered Na+ transport after an intracellular alpha-subunit deletion reveals strict external sequential release of Na+ from the Na/K pump.
2009,
Pubmed
,
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