ArticleeLife2016
The selectivity of the Na(+)/K(+)-pump is controlled by binding site protonation and self-correcting occlusion.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Active conformations of neuronal NaNature communications · 2026Article
- Exploring the Mechanism of NabioRxiv : the preprint server for biology · 2026Article
- On the mechanism of K+ transport through the inter-subunit tunnel of KdpFABC.The Journal of general physiology · 2026Article
- Derivatization of Bufadienolides at Carbon-3 of the Steroid Core and Their Consequences for the Interaction with NaInternational journal of molecular sciences · 2025Article
- The Quaternary Structure of the Sodium Pump Regulatory Complex Is Altered by Mutations of a Site Associated with Familial Hemiplegic Migraine.Molecular neurobiology · 2025Article
- Multistate Kinetic Model of the Sodium-Potassium ATPase.The journal of physical chemistry. B · 2025Article
- Insights into stereoselective ring formation in canonical strigolactone: Identification of a dirigent domain-containing enzyme catalyzing orobanchol synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multistate Method to Efficiently Account for Tautomerism and Protonation in Alchemical Free-Energy Calculations.Journal of chemical theory and computation · 2024Article
- Living Cell as a Self-Synchronized Chemical Reactor.The journal of physical chemistry letters · 2024Review
- Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.European journal of human genetics : EJHG · 2024Article
- Specific protonation of acidic residues confers KThe Journal of biological chemistry · 2024Article
- A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The NaBiophysical reviews · 2023Review
- Structure and function of HNature communications · 2022Article
- Fluorescence lifetime imaging microscopy reveals sodium pump dimers in live cells.The Journal of biological chemistry · 2022Article
- Stable potassium isotopes (Frontiers in physiology · 2022Article
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- NaMolecules (Basel, Switzerland) · 2021Review
- Evolution of Plant NaPlants (Basel, Switzerland) · 2021Article
- Effect of Endotoxemia Induced by Intraperitoneal Injection of Lipopolysaccharide on the Mg isotopic Composition of Biofluids and Tissues in Mice.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The Na(+)/K(+)-pump maintains the physiological K(+) and Na(+) electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle.
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