title: Crystal structure of the sodium-potassium pump at 2.4 A resolution.
abstract: 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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Shinoda
authors.forename: Haruo
authors.initials: H
authors.lastname: Ogawa
authors.forename: Flemming
authors.initials: F
authors.lastname: Cornelius
authors.forename: Chikashi
authors.initials: C
authors.lastname: Toyoshima
mesh_terms: D000818:Animals; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D005459:Fluorides / Q000378:metabolism; D006801:Humans; D017616:Magnesium Compounds / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012491:Salt Gland / Q000201:enzymology; D012754:Sharks; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism; D013552:Swine
chemical_list: D017616:Magnesium Compounds; D008565:Membrane Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; C069141:phospholemman; C031288:magnesium fluoride; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D005459:Fluorides; D011188:Potassium