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Structural determinants of water permeation through aquaporin-1

Nature volume 407, pages 599–605 (2000)Cite this article

Abstract

Human red cell AQP1 is the first functionally defined member of the aquaporin family of membrane water channels. Here we describe an atomic model of AQP1 at 3.8 Å resolution from electron crystallographic data. Multiple highly conserved amino-acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3 Å over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding puzzle in physiology—how membranes can be freely permeable to water but impermeable to protons.

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Figure 1: Representative areas of the AQP1 potential map with the fitted atomic model.
Figure 2: Ribbon representations of the AQP1 fold depicting the six membrane-spanning helices, the two pore helices, and the connecting loops in different colours.
Figure 3: Schematic representation of AQP1 topology and hydropathy.
Figure 4: Ribbon and space-filled diagrams representing the structure of the aqueous pore in AQP1.
Figure 5: Schematic representations explaining the mechanism for blocking proton permeation of AQP1.

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Acknowledgements

The authors thank B. L. Smith for technical assistance. These studies were partially carried out in the International Institute for Advanced Research, Matsushita Electric Industrial Co., Ltd. The research was supported by grants from the Japan Society for the Promotion of Science (JSPS), US National Institutes of Health, the Maurice E. Müller Foundation, the Swiss National Foundation for Scientific Research, and the European Union.

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Author notes

  1. Kazuyoshi Murata, Kaoru Mitsuoka, Teruhisa Hirai, J. Bernard Heymann and Andreas Engel: These authors contributed equally to this work.

Authors and Affiliations

  1. National Institute for Physiological Sciences, Okazaki, 444-8585, Japan

    Kazuyoshi Murata

  2. Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan

    Kaoru Mitsuoka, Teruhisa Hirai & Yoshinori Fujiyoshi

  3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115-5730, Massachusetts, USA

    Thomas Walz

  4. Departments of Biological Chemistry and Medicine, Johns Hopkins University School of Medicine, Baltimore , 21205-2185, Maryland, USA

    Peter Agre

  5. M. E. Müller-Institute for Microscopy at the Biozentrum, University of Basel, Basel, CH-4056 , Switzerland

    J. Bernard Heymann & Andreas Engel

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  1. Kazuyoshi Murata
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Correspondence to Yoshinori Fujiyoshi.

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Murata, K., Mitsuoka, K., Hirai, T. et al. Structural determinants of water permeation through aquaporin-1. Nature 407, 599–605 (2000). https://doi.org/10.1038/35036519

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