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

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-AlF 4 − trapped Na + -occluded (E1•P-ADP), BeF 3 − trapped exoplasmic side-open (E2P) and MgF 4 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.