Forschung & Innovation
Publikationen
Structural basis for gating mechanism of the human sodium-potassium pump
PMU Autor*in
Christine Deisl
Alle Autor*innen
Phong T Nguyen, Christine Deisl, Michael Fine, Trevor S Tippetts, Emiko Uchikawa, Xiao-Chen Bai, Beth Levine
Fachzeitschrift
Nature Communications
Kurzfassung
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 MgF42- trapped K+-occluded (E2•Pi) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na+/K+-ATPase.
Keywords
Humans, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Cryoelectron Microscopy, Ions, Potassium/metabolism, Sodium/metabolism, Sodium-Potassium-Exchanging ATPase/metabolism