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A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps

Nature Reviews Molecular Cell Biology volume 12, pages 60–70 (2011)Cite this article

Subjects

Key Points

  • Ions are transported across the plasma membrane by molecular pumps to generate chemical gradients and regulate pH or cell growth.

  • P-type ATPases are a family of molecular pumps that transport cations in or outside the cell. Members of this family include the Na+,K+-ATPase (found in animals) and the H+-ATPase (found in plants and fungi). The Na+,K+-ATPase exchanges Na+ for K+ and the H+-ATPase pumps H+ out of the cell.

  • P-type ATPases undergo conformational changes as part of their functional cycle, giving rise to two enzymatic states, E1 and E2, with different affinities for the primary transported ions.

  • P-type ATPases contain a cytoplasmic core comprising the phosphorylation, nucleotide-binding and actuator domains. These carry out autophosphatase activities and are responsible for ATP hydrolysis.

  • All P-type ATPases have six transmembrane helices (M1–M6). The Na+,K+-ATPase and the H+-ATPase have additional transmembrane helices (M7–M10) that may provide specificity or stability in the Na+,K+-ATPase and the H+-ATPase, respectively.

  • Many P-type ATPases also have regulatory domains that fine-tune their activity in ion pumping.

  • Crystal structures and functional studies of the Na+,K+-ATPase and the H+-ATPase have provided insight into their mechanisms of action in eukaryotic cells.

Abstract

Plasma membrane ATPases are primary active transporters of cations that maintain steep concentration gradients. The ion gradients and membrane potentials derived from them form the basis for a range of essential cellular processes, in particular Na+-dependent and proton-dependent secondary transport systems that are responsible for uptake and extrusion of metabolites and other ions. The ion gradients are also both directly and indirectly used to control pH homeostasis and to regulate cell volume. The plasma membrane H+-ATPase maintains a proton gradient in plants and fungi and the Na+,K+-ATPase maintains a Na+ and K+ gradient in animal cells. Structural information provides insight into the function of these two distinct but related P-type pumps.

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Figure 1: P-type ATPases energize the plasma membrane.
Figure 2: Structure and domain organization of P-type ATPases.
Figure 3: Ion-binding sites of Na+,K+-ATPase and H+-ATPase.
Figure 4: Autoinhibition of H+-ATPase function.

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Acknowledgements

We are grateful to H. Poulsen, A. T. Fuglsang, J. Vuust Møller and N. Fedosova for valuable discussions.

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Author notes

  1. Bjørn P. Pedersen

    Present address: Present address: Macromolecular Structure Group, Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.,

Authors and Affiliations

  1. Danish National Research Foundation, Centre for Membrane Pumps in Cells and Disease — PUMPKIN,

    J. Preben Morth, Bjørn P. Pedersen, Morten J. Buch-Pedersen, Jens Peter Andersen, Bente Vilsen, Michael G. Palmgren & Poul Nissen

  2. Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000, Aarhus, Denmark

    J. Preben Morth, Bjørn P. Pedersen & Poul Nissen

  3. Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, P.O. Box 1125, Blindern, N-0317, Olso, Norway

    J. Preben Morth

  4. Institute for Experimental Medical Research, Oslo University Hospital Ullevaal, 0407, Oslo, Norway

    J. Preben Morth

  5. Department of Plant Biology and Biotechnology, Plant Physiology and Anatomy Laboratory, University of Copenhagen, Thorvaldsensvej 40, DK-1871, Frederiksberg, Denmark

    Morten J. Buch-Pedersen & Michael G. Palmgren

  6. Department of Physiology and Biophysics, University of Aarhus, Ole Worms Allé 6, blg. 1180, DK-8000, Aarhus C, Denmark

    Jens Peter Andersen & Bente Vilsen

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DATABASES

PROSITE

PS00154

Protein Data Bank

3KDP

2ZXE

3BA6

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Glossary

Membrane potential

The voltage across a biological membrane; typically negative on the cytoplasmic side.

Proton-motive force

The proton potential that is established by the electrochemical gradient of protons across a biological membrane.

Post–Albers cycle

The reaction cycle of P-type ATPases: as cyclical changes between the E1 and E2 states associated with phosphoenzyme intermediates, E1P and E2P. Named after Robert L. Post and Wayne Albers.

Vectorial ion transport

Transport of ions that leads to a non-uniform distribution of ions across the plasma membrane.

Uncoupling

ATPase activity that is uncoupled from function. For P-type ATPases, uncoupling leads to ATPase activity without ion transport.

Half-channel

A gated channel structure that spans approximately half of the membrane bilayer and leads to a central binding site.

Coordination of cations

The side chain carbonyls, or the functional groups of the side chains with a free pair of electrons, can act as ligands to the central transported cation and thus coordinate the cations in a coordination complex.

Cation-π interaction

A non-covalent interaction between an electron-rich -system and a nearby cation. Frequently observed in protein structures between aromatic side chains (Phe, Tyr or Trp) and positively charged side chains (Lys or Arg) or bound cations.

14-3-3 protein

A member of a conserved family of eukaryotic regulatory proteins that interact with a diverse range of target proteins such as kinases, phosphatases, and transmembrane receptors and pumps.

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Morth, J., Pedersen, B., Buch-Pedersen, M. et al. A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps. Nat Rev Mol Cell Biol 12, 60–70 (2011). https://doi.org/10.1038/nrm3031

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