Publication Date:
2009-05-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinoda, Takehiro -- Ogawa, Haruo -- Cornelius, Flemming -- Toyoshima, Chikashi -- England -- Nature. 2009 May 21;459(7245):446-50. doi: 10.1038/nature07939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458722" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Binding Sites
;
Calcium-Transporting ATPases/chemistry/metabolism
;
Crystallography, X-Ray
;
Fluorides/metabolism
;
Humans
;
Magnesium Compounds/metabolism
;
Membrane Proteins/chemistry/metabolism
;
Models, Molecular
;
Phosphoproteins/chemistry/metabolism
;
Phosphorylation
;
Potassium/metabolism
;
Protein Conformation
;
Protein Subunits/chemistry/metabolism
;
Salt Gland/enzymology
;
Sharks
;
Sodium-Potassium-Exchanging ATPase/*chemistry/metabolism
;
Swine
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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