Journal Article

Crystal structure of the sodium–potassium pump at 2.4 Å resolution

Ogawa, Haruo, Cornelius, Flemming, Shinoda, Takehiro, Toyoshima, Chikashi

2009

Overview

Na + , K + -ATPase structure The sodium-potassium ATPase is an ATP-powered ion pump that creates concentration gradients for sodium and potassium ions across the plasma membrane of animal cells. Sodium ions are exported from the cell while potassium ions are imported producing gradients that are used for many essential processes, such as the action potentials of nerve cells. The crystal structure of this protein from shark rectal gland — highly homologous to the human version — has now been determined at 2.4 Å resolution. The structure helps elucidate many details of the protein's mechanism of action and will contribute, among other things, to the understanding and treatment of heart disease, since cardiac glycosides are inhibitors of the sodium-potassium pump. The sodium–potassium ATPase is an ATP-powered ion pump that creates concentration gradients for sodium and potassium ions across the plasma membrane of animal cells, a process essential, for example, in the action potentials of nerve cells. Here the crystal structure of the sodium–potassium pump in the shark, which is highly homologous to the human pump, is described. 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 1 , 2 . 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 α- and β-subunits and a regulatory FXYD protein 3 , 4 , 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 Å resolution 5 . Clearly visualized now at 2.4 Å 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 β-subunit has a critical role in K + binding (although its involvement has previously been suggested 6 , 7 , 8 ) and explains, at least partially, why the homologous Ca 2+ -ATPase counter-transports H + rather than K + , despite the coordinating residues being almost identical.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adenosine triphosphatase / Analysis / Animals / Binding Sites / Biological and medical sciences / Calcium-Transporting ATPases - chemistry / Calcium-Transporting ATPases - metabolism / Crystal structure / Crystalline structure / Crystallography, X-Ray / Crystals / Fluorides - metabolism / Fundamental and applied biological sciences. Psychology / Humanities and Social Sciences / Humans / Hydrogen bonds / letter / Magnesium Compounds - metabolism / Membrane Proteins - chemistry / Membrane Proteins - metabolism / Models, Molecular / Molecular biophysics / multidisciplinary / Phosphoproteins - chemistry / Phosphoproteins - metabolism / Phosphorylation / Physiological aspects / Potassium / Potassium - metabolism / Protein Conformation / Protein Subunits - chemistry / Protein Subunits - metabolism / Salt Gland - enzymology / Science / Science (multidisciplinary) / Sharks / Sodium / Sodium-Potassium-Exchanging ATPase - chemistry / Sodium-Potassium-Exchanging ATPase - metabolism / Structure / Structure in molecular biology / Swine