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The three-dimensional structure of aquaporin-1

Nature volume 387, pages 624–627 (1997)Cite this article

Abstract

The entry and exit of water from cells is a fundamental process of life. Recognition of the high water permeability of red blood cells led to the proposal that specialized water pores exist in the plasma membrane1. Expression in Xenopus oocytes and functional studies of an erythrocyte integral membrane protein of relative molecular mass 28,000, identified it as the mercury-sensitive water channel, aquaporin-1 (AQP1)2. Many related proteins, all belonging to the major intrinsic protein (MIP) family, are found throughout nature3. AQP1 is a homotetramer containing four independent aqueous channels4,5,6. When reconstituted into lipid bilayers, the protein forms two-dimensional lattices with a unit cell containing two tetramers in opposite orientation7,8,9,10. Here we present the three-dimensional structure of AQP1 determined at 6Å resolution by cryo-electron microscopy. Each AQP1 monomer has six tilted, bilayer-spanning α-helices which form a right-handed bundle surrounding a central density. These results, together with functional studies, provide a model that identifies the aqueous pore in the AQP1 molecule and indicates the organization of the tetrameric complex in the membrane.

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Figure 1: The unit cell of two-dimensional AQP1 crystals has a side length of 96Å and houses eight asymmetric units that form two tetramers integrated into the bilayer in opposite orientations.
Figure 2: Top, AQP1 monomer as seen a, from the extracellular side, and b, after a clockwise rotation around the x-axis by 45.

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Acknowledgements

This work has been supported by the Swiss National Foundation for Scientific Research, the Maurice E. Müller Foundation of Switzerland, the State of Basel, the National Institutes of Health, and the Japan Society for the Promotion of Science-Research for the Future Program. T.W. Thanks the EMBO for a fellowship.

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Author notes

  1. Thomas Walz, Barbara L. Smith & Peter Agre

    Present address: ¶Departments of Biological Chemistry and Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205-2185, Maryland, USA

Authors and Affiliations

  1. *M. E. Mller-Institute for Microscopic Structural Biology at the Biozentrum, University of Basel, CH-4056, Basel, Switzerland

    Thomas Walz, J. Bernard Heymann & Andreas Engel

  2. ‡International Institute for Advanced Research, Matsushita Electric Industrial Co., Ltd., 3-4 Hikaridai, 619-02, Seika, Japan

    Teruhisa Hirai, Kazuyoshi Murata & Kaoru Mitsuoka

  3. §Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-Ku, 606-01, Kyoto, Japan

    Yoshinori Fujiyoshi

  4. Krebs Institute for Biomolecular Biology, Department of Molecular Biology and Biotechnology, University of Sheffield, PO Box 594, Sheffield, S10 2UH, UK

    Thomas Walz

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Walz, T., Hirai, T., Murata, K. et al. The three-dimensional structure of aquaporin-1. Nature 387, 624–627 (1997). https://doi.org/10.1038/42512

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