Crystal Structure of Na⁺, K⁺-ATPase in the Na⁺-Bound State

The Na⁺, K⁺—adenosine triphosphatase (ATPase) maintains the electrochemical gradients of Na⁺ and K⁺ across the plasma membrane—a prerequisite for electrical excitability and secondary transport. Hitherto, structural information has been limited to K⁺-bound or ouabain-blocked forms. We present the crystal structure of a Na⁺-bound Na⁺, K⁺-ATPase as determined at 4.3 Å resolution. Compared with the K⁺-bound form, large conformational changes are observed in the α subunit whereas the β and γ subunit structures are maintained. The locations of the three Na⁺ sites are indicated with the unique site III at the recently suggested IIIb, as further supported by electrophysiological studies on leak currents. Extracellular release of the third Na⁺ from IIIb through IIIa, followed by exchange of Na⁺ for K⁺ at sites I and II, is suggested.