Cartoon showing the normal 3 Na+/2 K+ transport cycle of the Na+,K+-ATPase modeled as an integral membrane cation channel that incorporates two gates (bars in horizontal, closed, or vertical, open, positions) which never open simultaneously. The Na+/K+ pump exists in two major conformations: E1 (lower row), with binding sites accessible from the cell interior (labeled "In"), and E2 (upper row), with binding sites accessible from the exterior (labeled "Out"). Binding of the third intracellular Na+ ion (accompanied by phosphorylation), or of the second extracellular K+ ion (accompanied by dephosphorylation), shuts the cytoplasmic, or extracellular gate, respectively, forming occluded states (top right and bottom left) in which the ions are enclosed within the protein. In each case, a subsequent major conformational change opens the opposite gate, releasing the transported ions; for K+, this deocclusion step is accelerated by binding of the ATP that later phosphorylates the pump.

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