Structural Basis for Gating Mechanism of the Human Sodium-potassium Pump

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 8

PMID 36075933

Authors

Phong T Nguyen

Christine Deisl

Michael Fine

Trevor S Tippetts

Emiko Uchikawa

Xiao-Chen Bai

Beth Levine

Affiliations

Soon will be listed here.

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-AlF trapped Na-occluded (E1•P-ADP), BeF trapped exoplasmic side-open (E2P) and MgF trapped K-occluded (E2•P) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na/K-ATPase.

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