Electrostatic Stabilization Plays a Central Role in Autoinhibitory Regulation of the Na+,K+-ATPase
| Autor: | Hans-Jürgen Apell, Minwoo Han, Qiucen Jiang, Alvaro Garcia, Ronald J. Clarke, Himanshu Khandelia, Flemming Cornelius |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
PARTICLE MESH EWALD Protein Conformation Swine ATPase 01 natural sciences SODIUM-POTASSIUM PUMP P-TYPE ATPASES Adenosine Triphosphate Guoy-Chapman theory CRYSTAL-STRUCTURE Channels and Transporters Phosphorylation KIDNEY OUTER MEDULLA buffer effects chemistry.chemical_classification 010304 chemical physics biology Chemistry ADDITIVE FORCE-FIELD Membrane eosin fluorescence Sodium-Potassium-Exchanging ATPase ALPHA-SUBUNIT ionic strength Stereochemistry Protein subunit Static Electricity Kinetics Biophysics Molecular Dynamics Simulation 03 medical and health sciences ddc:570 0103 physical sciences Animals PROTEIN-KINASE-C Na+/K+-ATPase Osmolar Concentration 030104 developmental biology Enzyme MOLECULAR-DYNAMICS Ionic strength biology.protein GUI MEMBRANE-BUILDER 030403 - Characterisation of Biological Macromolecules [FoR] stopped-flow kinetics |
| Zdroj: | Jiang, 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, vol. 112, no. 2, pp. 288-299 . https://doi.org/10.1016/j.bpj.2016.12.008 Jiang, 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, vol. 112, no. 2, pp. 288-299 . https://doi.org/10.1016/j.bpj.2016.12.008 |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2016.12.008 |
| Popis: | 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. published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|