Powered by LatticeGrid

Search Enter term and hit return. Use '*' for as a wildcard.
Razavi AM, Delemotte L, Berlin JR, Carnevale V, Voelz VA
Molecular simulations and free-energy calculations suggest conformation-dependent anion binding to a cytoplasmic site as a mechanism for Na+/K+-ATPase ion selectivity
J Biol Chem (2017) 292:12412-12423.
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 D926. 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.
Publication Date: 2017-07-28.
PMCID: PMC5535017
Last updated on Tuesday, June 05, 2018