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for updates. The development team can be contacted at datacentre@scilifelab.se
if you have any question.Razavi AM, Delemotte L, Berlin JR, Carnevale V, Voelz VA
J Biol Chem 292 (30) 12412-12423 [2017-07-28; online 2017-06-06]
Na+/K+-ATPase transports Na+ and K+ ions across the cell membrane via an ion-binding site becoming alternatively accessible to the intra- and extracellular milieu by conformational transitions that confer marked changes in ion-binding stoichiometry and selectivity. To probe the mechanism of these changes, we used molecular simulation and free-energy perturbation approaches to identify probable protonation states of Na+- and K+-coordinating residues in E1P and E2P conformations of Na+/K+-ATPase. Analysis of these simulations revealed a molecular mechanism responsible for the change in protonation state: the conformation-dependent binding of an anion (a chloride ion in our simulations) to a previously unrecognized cytoplasmic site in the loop between transmembrane helices 8 and 9, which influences the electrostatic potential of the crucial Na+-coordinating residue Asp926 This mechanistic model is consistent with experimental observations and provides a molecular-level picture of how E1P to E2P enzyme conformational transitions are coupled to changes in ion-binding stoichiometry and selectivity.
PubMed 28588025
DOI 10.1074/jbc.M117.779090
Crossref 10.1074/jbc.M117.779090
pii: S0021-9258(20)39622-8
pmc: PMC5535017
PDB: 2ZXE
PDB: 3KDP
PDB: 4HQJ
PDB: 3WGU