Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na+,K+-ATPase

Jiang, Q; Garcia, A; Han, M; Cornelius, F; Apell, HJ; Khandelia, H; Clarke, RJ

Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na+,K+-ATPase

Jiang, Q Garcia, A

Han, M Cornelius, F

Apell, HJ Khandelia, H

Clarke, RJ

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Publication Type:: Journal Article
Citation:: Biophysical Journal, 2017, 112 (2), pp. 288 - 299
Issue Date:: 2017-01-24

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Field	Value	Language
dc.contributor.author	Jiang, Q	en_US
dc.contributor.author	Garcia, A https://orcid.org/0000-0002-1159-4567	en_US
dc.contributor.author	Han, M	en_US
dc.contributor.author	Cornelius, F https://orcid.org/0000-0003-1566-0020	en_US
dc.contributor.author	Apell, HJ	en_US
dc.contributor.author	Khandelia, H https://orcid.org/0000-0001-9913-6394	en_US
dc.contributor.author	Clarke, RJ https://orcid.org/0000-0002-0950-8017	en_US
dc.date.available	2016-12-05	en_US
dc.date.issued	2017-01-24	en_US
dc.identifier.citation	Biophysical Journal, 2017, 112 (2), pp. 288 - 299	en_US
dc.identifier.issn	0006-3495	en_US
dc.identifier.uri	http://hdl.handle.net/10453/123980
dc.description.abstract	© 2017 Biophysical Society The Na+,K+-ATPase is present in the plasma membrane of all animal cells. It plays a crucial role in maintaining the Na+ and K+ electrochemical potential gradients across the membrane, which are essential in numerous physiological processes, e.g., nerve, muscle, and kidney function. Its cellular activity must, therefore, be under tight metabolic control. Consideration of eosin fluorescence and stopped-flow kinetic data indicates that the enzyme's E2 conformation is stabilized by electrostatic interactions, most likely between the N-terminus of the protein's catalytic α-subunit and the adjacent membrane. The electrostatic interactions can be screened by increasing ionic strength, leading to a more evenly balanced equilibrium between the E1 and E2 conformations. This represents an ideal situation for effective regulation of the Na+,K+-ATPase's enzymatic activity, because protein modifications, which perturb this equilibrium in either direction, can then easily lead to activation or inhibition. The effect of ionic strength on the E1:E2 distribution and the enzyme's kinetics can be mathematically described by the Gouy-Chapman theory of the electrical double layer. Weakening of the electrostatic interactions and a shift toward E1 causes a significant increase in the rate of phosphorylation of the enzyme by ATP. Electrostatic stabilization of the Na+,K+-ATPase's E2 conformation, thus, could play an important role in regulating the enzyme's physiological catalytic turnover.	en_US
dc.relation.ispartof	Biophysical Journal	en_US
dc.relation.isbasedon	10.1016/j.bpj.2016.12.008	en_US
dc.subject.classification	Biophysics	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Swine	en_US
dc.subject.mesh	Adenosine Triphosphate	en_US
dc.subject.mesh	Protein Conformation	en_US
dc.subject.mesh	Phosphorylation	en_US
dc.subject.mesh	Osmolar Concentration	en_US
dc.subject.mesh	Sodium-Potassium-Exchanging ATPase	en_US
dc.subject.mesh	Static Electricity	en_US
dc.subject.mesh	Molecular Dynamics Simulation	en_US
dc.title	Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na<sup>+</sup>,K<sup>+</sup>-ATPase	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	112	en_US
utslib.for	0203 Classical Physics	en_US
utslib.for	0301 Analytical Chemistry	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	02 Physical Sciences	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	112	en_US

Abstract:

© 2017 Biophysical Society The Na+,K+-ATPase is present in the plasma membrane of all animal cells. It plays a crucial role in maintaining the Na+ and K+ electrochemical potential gradients across the membrane, which are essential in numerous physiological processes, e.g., nerve, muscle, and kidney function. Its cellular activity must, therefore, be under tight metabolic control. Consideration of eosin fluorescence and stopped-flow kinetic data indicates that the enzyme's E2 conformation is stabilized by electrostatic interactions, most likely between the N-terminus of the protein's catalytic α-subunit and the adjacent membrane. The electrostatic interactions can be screened by increasing ionic strength, leading to a more evenly balanced equilibrium between the E1 and E2 conformations. This represents an ideal situation for effective regulation of the Na+,K+-ATPase's enzymatic activity, because protein modifications, which perturb this equilibrium in either direction, can then easily lead to activation or inhibition. The effect of ionic strength on the E1:E2 distribution and the enzyme's kinetics can be mathematically described by the Gouy-Chapman theory of the electrical double layer. Weakening of the electrostatic interactions and a shift toward E1 causes a significant increase in the rate of phosphorylation of the enzyme by ATP. Electrostatic stabilization of the Na+,K+-ATPase's E2 conformation, thus, could play an important role in regulating the enzyme's physiological catalytic turnover.

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http://hdl.handle.net/10453/123980

Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na<sup>+</sup>,K<sup>+</sup>-ATPase