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Crystal structure of the sodium–potassium pump at 2.4 Å resolution

Nature volume 459, pages 446–450 (2009)Cite this article

Abstract

Sodium–potassium ATPase is an ATP-powered ion pump that establishes concentration gradients for Na+ and K+ ions across the plasma membrane in all animal cells by pumping Na+ from the cytoplasm and K+ from the extracellular medium1,2. Such gradients are used in many essential processes, notably for generating action potentials. Na+, K+-ATPase is a member of the P-type ATPases, which include sarcoplasmic reticulum Ca2+-ATPase and gastric H+, K+-ATPase, among others, and is the target of cardiac glycosides. Here we describe a crystal structure of this important ion pump, from shark rectal glands, consisting of α- and β-subunits and a regulatory FXYD protein3,4, all of which are highly homologous to human ones. The ATPase was fixed in a state analogous to E2·2K+·Pi, in which the ATPase has a high affinity for K+ and still binds Pi, as in the first crystal structure of pig kidney enzyme at 3.5 Å resolution5. Clearly visualized now at 2.4 Å resolution are coordination of K+ and associated water molecules in the transmembrane binding sites and a phosphate analogue (MgF42-) in the phosphorylation site. The crystal structure shows that the β-subunit has a critical role in K+ binding (although its involvement has previously been suggested6,7,8) and explains, at least partially, why the homologous Ca2+-ATPase counter-transports H+ rather than K+, despite the coordinating residues being almost identical.

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Figure 1: Architecture of Na+, K+-ATPase with bound MgF42- and K+.
Figure 2: Superimposition of the crystal structure of Na + , K + -ATPase on that of Ca 2+ -ATPase.
Figure 3: Transmembrane K + -binding sites.
Figure 4: Interactions among the α- and β- subunits and the FXYD protein at the extracellular surface of the membrane.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Atomic coordinates and structure factors for the structure reported in this work have been deposited in the Protein Data Bank under accession number 2ZXE.

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Acknowledgements

We thank M. Kawamoto and N. Shimizu for their help in data collection at BL41XU, SPring-8, and T. Tsuda for many aspects of this work. We are grateful to D. B. McIntosh for his help in improving the manuscript and H. R.Z. Christensen for technical assistance. Thanks are also due to G. Cramb for sharing sequencing results of the β-subunit with us before publication. This work was supported by a Specially Promoted Project Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan, to C.T., and grants from the Danish Medical Research Council, to F.C.

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan ,

    Takehiro Shinoda, Haruo Ogawa & Chikashi Toyoshima

  2. Department of Physiology and Biophysics, University of Aarhus, DK-8000 Aarhus C, Denmark

    Flemming Cornelius

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  1. Takehiro Shinoda
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  2. Haruo Ogawa
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  3. Flemming Cornelius
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  4. Chikashi Toyoshima
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Correspondence to Chikashi Toyoshima.

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Shinoda, T., Ogawa, H., Cornelius, F. et al. Crystal structure of the sodium–potassium pump at 2.4 Å resolution. Nature 459, 446–450 (2009). https://doi.org/10.1038/nature07939

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