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

Author

Listed:
  • Phong T. Nguyen

    (University of Texas Southwestern Medical Center)

  • Christine Deisl

    (University of Texas Southwestern Medical Center)

  • Michael Fine

    (University of Texas Southwestern Medical Center)

  • Trevor S. Tippetts

    (University of Texas Southwestern Medical Center)

  • Emiko Uchikawa

    (University of Texas Southwestern Medical Center)

  • Xiao-chen Bai

    (University of Texas Southwestern Medical Center)

  • Beth Levine

    (University of Texas Southwestern Medical Center)

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 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.

Suggested Citation

  • Phong T. Nguyen & Christine Deisl & Michael Fine & Trevor S. Tippetts & Emiko Uchikawa & Xiao-chen Bai & Beth Levine, 2022. "Structural basis for gating mechanism of the human sodium-potassium pump," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32990-x
    DOI: 10.1038/s41467-022-32990-x
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    References listed on IDEAS

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    3. Ryuta Kanai & Haruo Ogawa & Bente Vilsen & Flemming Cornelius & Chikashi Toyoshima, 2013. "Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state," Nature, Nature, vol. 502(7470), pages 201-206, October.
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