3N23

Crystal structure of the high affinity complex between ouabain and the E2P form of the sodium-potassium pump

Summary for 3N23

• Entry DOI: 10.2210/pdb3n23/pdb
• Related: 3B9B 3KDP 3N2F
• Descriptor: Sodium/potassium-transporting ATPase subunit alpha-1, Sodium/potassium-transporting ATPase subunit beta-1, Na+/K+ ATPase gamma subunit transcript variant a, ... (5 entities in total)
• Functional Keywords: sodium-potassium pump, p-type atpase, ouabain, cardiotonic steroids, hydrolase
• Biological source: Sus scrofa (pigs); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P05024; Cell membrane; Single-pass type II membrane protein: P05027
• Total number of polymer chains: 6
• Total formula weight: 291749.44

Authors

Yatime, L.,Laursen, M.,Morth, J.P.,Esmann, M.,Nissen, P.,Fedosova, N.U. (deposition date: 2010-05-17, release date: 2011-01-19, Last modification date: 2014-09-17)

Primary citation

Yatime, L.,Laursen, M.,Morth, J.P.,Esmann, M.,Nissen, P.,Fedosova, N.U.
Structural insights into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase.
J.Struct.Biol., 174:296-306, 2011

PubMed Abstract: 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 Å 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 αM1-αM6, 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 αM1-2 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.

PubMed: 21182963
DOI: 10.1016/j.jsb.2010.12.004

Experimental method

X-RAY DIFFRACTION (4.6 Å)