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

Phong T Nguyen; Christine Deisl; Michael Fine; Trevor S Tippetts; Emiko Uchikawa; Xiao-Chen Bai; Beth Levine

doi:10.1038/s41467-022-32990-x

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

Phong T Nguyen, Christine Deisl (Co-author), Michael Fine, Trevor S Tippetts, Emiko Uchikawa, Xiao-Chen Bai, Beth Levine

Research output: Contribution to journal › Original Article › peer-review

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.

Original language	English
Pages (from-to)	5293
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32990-x
Publication status	Published - 8 Sept 2022
Externally published	Yes

Keywords

Adenosine Diphosphate
Adenosine Triphosphate
Animals
Cryoelectron Microscopy
Humans
Ions
Potassium/metabolism
Sodium/metabolism
Sodium-Potassium-Exchanging ATPase/metabolism

Access to Document

10.1038/s41467-022-32990-x

Cite this

@article{75d651a932da4bbdbbfa7a3cf62f0723,

title = "Structural basis for gating mechanism of the human sodium-potassium pump",

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.",

keywords = "Adenosine Diphosphate, Adenosine Triphosphate, Animals, Cryoelectron Microscopy, Humans, Ions, Potassium/metabolism, Sodium/metabolism, Sodium-Potassium-Exchanging ATPase/metabolism",

author = "Nguyen, {Phong T} and Christine Deisl and Michael Fine and Tippetts, {Trevor S} and Emiko Uchikawa and Xiao-Chen Bai and Beth Levine",

note = "Deisl: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA",

year = "2022",

month = sep,

day = "8",

doi = "10.1038/s41467-022-32990-x",

language = "English",

volume = "13",

pages = "5293",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "NATURE PORTFOLIO",

number = "1",

}

TY - JOUR

T1 - Structural basis for gating mechanism of the human sodium-potassium pump

AU - Nguyen, Phong T

AU - Deisl, Christine

AU - Fine, Michael

AU - Tippetts, Trevor S

AU - Uchikawa, Emiko

AU - Bai, Xiao-Chen

AU - Levine, Beth

N1 - Deisl: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA

PY - 2022/9/8

Y1 - 2022/9/8

N2 - 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.

AB - 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.

KW - Adenosine Diphosphate

KW - Adenosine Triphosphate

KW - Animals

KW - Cryoelectron Microscopy

KW - Humans

KW - Ions

KW - Potassium/metabolism

KW - Sodium/metabolism

KW - Sodium-Potassium-Exchanging ATPase/metabolism

U2 - 10.1038/s41467-022-32990-x

DO - 10.1038/s41467-022-32990-x

M3 - Original Article

C2 - 36075933

SN - 2041-1723

VL - 13

SP - 5293

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this