Crystal structure of the sodium-potassium pump at 2.4 A resolution

Nature. 2009 May 21;459(7245):446-50. doi: 10.1038/nature07939.


Sodium-potassium ATPase is an ATP-powered ion pump that establishes concentration gradients for Na(+) and K(+) ions across the plasma membrane in all animal cells by pumping Na(+) from the cytoplasm and K(+) from the extracellular medium. Such gradients are used in many essential processes, notably for generating action potentials. Na(+), K(+)-ATPase is a member of the P-type ATPases, which include sarcoplasmic reticulum Ca(2+)-ATPase and gastric H(+), K(+)-ATPase, among others, and is the target of cardiac glycosides. Here we describe a crystal structure of this important ion pump, from shark rectal glands, consisting of alpha- and beta-subunits and a regulatory FXYD protein, all of which are highly homologous to human ones. The ATPase was fixed in a state analogous to E2.2K(+).P(i), in which the ATPase has a high affinity for K(+) and still binds P(i), as in the first crystal structure of pig kidney enzyme at 3.5 A resolution. Clearly visualized now at 2.4 A resolution are coordination of K(+) and associated water molecules in the transmembrane binding sites and a phosphate analogue (MgF(4)(2-)) in the phosphorylation site. The crystal structure shows that the beta-subunit has a critical role in K(+) binding (although its involvement has previously been suggested) and explains, at least partially, why the homologous Ca(2+)-ATPase counter-transports H(+) rather than K(+), despite the coordinating residues being almost identical.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium-Transporting ATPases / chemistry
  • Calcium-Transporting ATPases / metabolism
  • Crystallography, X-Ray
  • Fluorides / metabolism
  • Humans
  • Magnesium Compounds / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Potassium / metabolism
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Salt Gland / enzymology
  • Sharks
  • Sodium-Potassium-Exchanging ATPase / chemistry*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Swine


  • Magnesium Compounds
  • Membrane Proteins
  • Phosphoproteins
  • Protein Subunits
  • phospholemman
  • magnesium fluoride
  • Calcium-Transporting ATPases
  • Sodium-Potassium-Exchanging ATPase
  • Fluorides
  • Potassium

Associated data

  • PDB/2ZXE