3n23

Publication Abstract from PubMed

The Na+,K+-ATPase belongs to the P-ATPase family, whose characteristic property is the formation of a phosphorylated intermediate. The enzyme is also a defined target for cardiotonic steroids which inhibit its functional activity and initiate intracellular signaling. Here we describe the 4.6 A resolution crystal structure of the pig kidney Na+,K+-ATPase in its phosphorylated form stabilized by high affinity binding of the cardiotonic steroid ouabain. The steroid binds to a site formed at transmembrane segments alphaM1-alphaM6, plugging the ion pathway from the extracellular side. This structure differs from the previously reported low affinity complex with potassium. Most importantly, the A domain has rotated in response to phosphorylation and alphaM1-2 move towards the ouabain molecule, providing for high affinity interactions and closing the ion pathway from the extracellular side. The observed re-arrangements of the Na+,K+-ATPase stabilized by cardiotonic steroids may affect protein-protein interactions within the intracellular signal transduction networks.

Structural insights into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase.,Yatime L, Laursen M, Morth JP, Esmann M, Nissen P, Fedosova NU J Struct Biol. 2011 May;174(2):296-306. doi: 10.1016/j.jsb.2010.12.004. Epub 2010, Dec 21. PMID:21182963^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.