Structural basis for gating mechanism of the human sodium-potassium pump.

Abstract

P2-type ATPase sodium-potassium pumps (Na⁺/K⁺-ATPases) are ion-transporting enzymes that use ATP to transport Na⁺ and K⁺ on opposite sides of the lipid bilayer against their electrochemical gradients to maintain ion concentration gradients across the membranes in all animal cells. Despite the available molecular architecture of the Na⁺/K⁺-ATPases, a complete molecular mechanism by which the Na⁺ and K⁺ ions access into and are released from the pump remains unknown. Here we report five cryo-electron microscopy (cryo-EM) structures of the human alpha3 Na⁺/K⁺-ATPase in its cytoplasmic side-open (E1), ATP-bound cytoplasmic side-open (E1•ATP), ADP-AlF₄^- trapped Na⁺-occluded (E1•P-ADP), BeF₃^- trapped exoplasmic side-open (E2P) and MgF₄^2- trapped K⁺-occluded (E2•P_i) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na⁺/K⁺-ATPase.