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, Michael Fine, Trevor S. Tippetts, Emiko Uchikawa, Xiao chen Bai, Beth Levine

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

5 Scopus citations

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•P_i) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na⁺/K⁺-ATPase.

Original language	English (US)
Article number	5293
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32990-x
State	Published - Dec 2022

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

Access to Document

10.1038/s41467-022-32990-x

Cite this

@article{49c3c9db087f4054a212b56214713809,

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.",

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

note = "Funding Information: This work is dedicated to the memory of Prof. Beth Levine. Beyond her invaluable scientific support, without which this work would not be possible, her kindness, encouragement, and devotion will have an indelible impact for generations of scientists to come. We thank Dr. Gabriele Meloni for critical reading of the manuscript. Cryo-EM data were collected at the University of Texas Southwestern Medical Center Cryo-EM Facility, which is funded by the CPRIT Core Facility Support Award RP170644. We thank D Stoddard for technical support and facility access. This work was supported in part by the Howard Hughes Medical Institute (to B.L.), the NIH (grant R01GM136976 to X.-C.B), the Welch Foundation (grant I-1944 to X.-C.B) the Virginia Murchison Linthicum Scholar in Medical Research fund (to X.-C.B). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

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

language = "English (US)",

volume = "13",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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 - Funding Information: This work is dedicated to the memory of Prof. Beth Levine. Beyond her invaluable scientific support, without which this work would not be possible, her kindness, encouragement, and devotion will have an indelible impact for generations of scientists to come. We thank Dr. Gabriele Meloni for critical reading of the manuscript. Cryo-EM data were collected at the University of Texas Southwestern Medical Center Cryo-EM Facility, which is funded by the CPRIT Core Facility Support Award RP170644. We thank D Stoddard for technical support and facility access. This work was supported in part by the Howard Hughes Medical Institute (to B.L.), the NIH (grant R01GM136976 to X.-C.B), the Welch Foundation (grant I-1944 to X.-C.B) the Virginia Murchison Linthicum Scholar in Medical Research fund (to X.-C.B). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

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.

UR - http://www.scopus.com/inward/record.url?scp=85137543706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85137543706&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-32990-x

DO - 10.1038/s41467-022-32990-x

M3 - Article

C2 - 36075933

AN - SCOPUS:85137543706

SN - 2041-1723

VL - 13

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5293

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this