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

Through cryo-EM analysis, here authors reveal conformational rearrangements that are critical for the gating mechanism of the human alpha3 Na+/K+-ATPase 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 center dot ATP), ADP-AlF4- trapped Na+-occluded (E1 center dot P-ADP), BeF3- trapped exoplasmic side-open (E2P) and MgF42- trapped K+-occluded (E2 center dot P-i) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na+/K+-ATPase.

Automated summary

Through cryo-EM analysis, the authors reveal critical conformational rearrangements in the gating mechanism of the human Na+/K+-ATPase, providing important insights into the molecular mechanism of ion transport.