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Crystal structure of the plasma membrane proton pump

Nature volume 450, pages 1111–1114 (2007)Cite this article

Abstract

A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H+-ATPase (the proton pump) in plants and fungi1,2,3, and Na+,K+-ATPase (the sodium–potassium pump) in animals4. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis5. The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na+,K+-ATPase and Ca2+-ATPase are type II6. Electron microscopy has revealed the overall shape of proton pumps7, however, an atomic structure has been lacking. Here we present the first structure of a P-type proton pump determined by X-ray crystallography. Ten transmembrane helices and three cytoplasmic domains define the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane where it is lined by conserved hydrophilic and charged residues. Proton transport against a high membrane potential is readily explained by this structural arrangement.

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Figure 1: Overall structure of the plasma membrane H + -ATPase.
Figure 2: Structural conservation of P-type ATPase architecture.
Figure 3: The intramembranous buried cavity and proton binding site of the plasma membrane H + -ATPase.
Figure 4: Mechanism of proton transport by plasma membrane H + -ATPase.

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Protein Data Bank

Data deposits

Coordinates and structure factors have been deposited in the Protein Data Bank with the accession number 3B8C.

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Acknowledgements

We thank T. L.-M. Sørensen for contributions to initial project design and E. Pohl, C. Schulze-Briese and T. Tomizaki for assistance with synchrotron data collection. We are grateful to A. M. Nielsen for technical assistance and L. Yatime for help with data collection. B.P.P. is supported by a PhD fellowship from the Graduate School of Science at the University of Aarhus, M.J.B-P. by a post-doctoral fellowship from the Carlsberg Foundation, J.P.M. by a post-doctoral fellowship from the DANSYNC programme of the Danish Research Council, and P.N. by a Hallas-Møller stipend from the Novo Nordisk Foundation.

Author Contributions B.P.P. performed crystallization experiments, collected and processed the data, and determined, refined and analysed the structure. M.J.B.-P. performed expression and protein purification, and later performed crystallization experiments and analysed the structure. J.P.M. assisted in data collection and processing. M.G.P. and P.N. contributed with equal resources, supervised the project and analysed the structure.

Author information

Author notes

  1. Bjørn P. Pedersen and Morten J. Buch-Pedersen: These authors contributed equally to this work.

Authors and Affiliations

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

    Bjørn P. Pedersen, Morten J. Buch-Pedersen, J. Preben Morth, Michael G. Palmgren & Poul Nissen

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

    Bjørn P. Pedersen, Morten J. Buch-Pedersen, J. Preben Morth & Poul Nissen

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

    Morten J. Buch-Pedersen & Michael G. Palmgren

Authors
  1. Bjørn P. Pedersen
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Corresponding authors

Correspondence to Michael G. Palmgren or Poul Nissen.

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Pedersen, B., Buch-Pedersen, M., Preben Morth, J. et al. Crystal structure of the plasma membrane proton pump. Nature 450, 1111–1114 (2007). https://doi.org/10.1038/nature06417

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