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dc.contributor.authorJiang, Qiucen
dc.contributor.authorGarcia, Alvaro
dc.contributor.authorHan, Minwoo
dc.contributor.authorCornelius, Flemming
dc.contributor.authorApell, Hans-Jurgen
dc.contributor.authorKhandelia, Himanshu
dc.contributor.authorClarke, Ronald J.
dc.date.accessioned2019-09-05T04:21:14Z
dc.date.available2019-09-05T04:21:14Z
dc.date.issued2017-01-24
dc.identifier.citationJiang, Q., Garcia, A., Han, M., Cornelius, F., Apell, H.-J., Khandelia, H., & Clarke, R. J. (2017). Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na + ,K + -ATPase. Biophysical Journal, 112(2), 288–299. https://doi.org/10.1016/j.bpj.2016.12.008en_AU
dc.identifier.urihttp://hdl.handle.net/2123/21028
dc.description.abstractThe 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, since 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 towards 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_AU
dc.description.sponsorshipAustralian Research Councilen_AU
dc.language.isoen_AUen_AU
dc.publisherElsevieren_AU
dc.relationARC DP121003548, ARC DP150101112en_AU
dc.rights© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 licenseen_AU
dc.subjecteosinen_AU
dc.subjectGuoy-Chapman theoryen_AU
dc.subjectstopped-flow kineticsen_AU
dc.subjectfluorescenceen_AU
dc.subjectionic strengthen_AU
dc.subjectbuffer effectsen_AU
dc.titleElectrostatic stabilization plays a central role in autoinhibitory regulation of the Na+,K+-ATPaseen_AU
dc.typeArticleen_AU
dc.subject.asrcFoR::030403 - Characterisation of Biological Macromoleculesen_AU
dc.identifier.doidx.doi.org/10.1016/j.bpj.2016.12.008
dc.type.pubtypePost-printen_AU


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