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Protonation of key acidic residues is critical for the K+-selectivity of the Na/K pump

Journal Article


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Abstract


  • The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na+ and K+ concentration gradients across the cell membrane. For each hydrolyzed ATP molecule, the pump extrudes three Na+ and imports two K+ by alternating between outward- and inward-facing conformations that preferentially bind K+ or Na+, respectively. Remarkably, the selective K+ and Na+ binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy–perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K+-loaded state (E2·Pi) reveal that protonation of the high-field acidic side chains involved in the binding sites is crucial to achieving the proper K+ selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K+ over Na+ is affected by extracellular pH.

Authors


  •   Yu, Haibo
  •   Ratheal, Ian (external author)
  •   Artigas, Pablo (external author)
  •   Roux, Benoit (external author)

Publication Date


  • 2011

Citation


  • Yu, H., Ratheal, I., Artigas, P. & Roux, B. (2011). Protonation of key acidic residues is critical for the K+-selectivity of the Na/K pump. Nature Structural and Molecular Biology, 18 (10), 1159-1163.

Scopus Eid


  • 2-s2.0-80455174602

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2138&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/1072

Has Global Citation Frequency


Number Of Pages


  • 4

Start Page


  • 1159

End Page


  • 1163

Volume


  • 18

Issue


  • 10

Place Of Publication


  • USA

Abstract


  • The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na+ and K+ concentration gradients across the cell membrane. For each hydrolyzed ATP molecule, the pump extrudes three Na+ and imports two K+ by alternating between outward- and inward-facing conformations that preferentially bind K+ or Na+, respectively. Remarkably, the selective K+ and Na+ binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy–perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K+-loaded state (E2·Pi) reveal that protonation of the high-field acidic side chains involved in the binding sites is crucial to achieving the proper K+ selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K+ over Na+ is affected by extracellular pH.

Authors


  •   Yu, Haibo
  •   Ratheal, Ian (external author)
  •   Artigas, Pablo (external author)
  •   Roux, Benoit (external author)

Publication Date


  • 2011

Citation


  • Yu, H., Ratheal, I., Artigas, P. & Roux, B. (2011). Protonation of key acidic residues is critical for the K+-selectivity of the Na/K pump. Nature Structural and Molecular Biology, 18 (10), 1159-1163.

Scopus Eid


  • 2-s2.0-80455174602

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2138&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/1072

Has Global Citation Frequency


Number Of Pages


  • 4

Start Page


  • 1159

End Page


  • 1163

Volume


  • 18

Issue


  • 10

Place Of Publication


  • USA