Structural highlights
Function
AT1A1_PIG This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
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.
See Also
References
- ↑ Yatime L, Laursen M, Morth JP, Esmann M, Nissen P, Fedosova NU. Structural insights into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase. J Struct Biol. 2011 May;174(2):296-306. doi: 10.1016/j.jsb.2010.12.004. Epub 2010, Dec 21. PMID:21182963 doi:http://dx.doi.org/10.1016/j.jsb.2010.12.004
