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Three-dimensional organization of a human water channel

Nature volume 387, pages 627–630 (1997)Cite this article

Abstract

Aquaporins (AQP) are members of the major intrinsic protein (MIP) superfamily of integral membrane proteins and facilitate water transport in various eukaryotes and prokaryotes1,2. The archetypal aquaporin AQP1 is a partly glycosylated water-selective channel3,4 that is widely expressed in the plasma membranes of several water-permeable epithelial and endothelial cells2,5. Here we report the three-dimensional structure of deglycosylated, human erythrocyte AQP1, determined at 7Å resolution in the membrane plane by electron crystallography of frozen-hydrated two-dimensional crystals6,7. The structure has an in-plane, intramolecular 2-fold axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer is composed of six membrane-spanning, tilted α-helices. These helices form a barrel that encloses a vestibular region leading to the water-selective channel, which is outlined by densities attributed to the functionally important NPA boxes8 and their bridges to the surrounding helices. The intramolecular symmetry within the AQP1 molecule represents a new motif for the topology and design of membrane protein channels, and is a simple and elegant solution to the problem of bidirectional transport across the bilayer.

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Figure 1: Stereo pair of the three-dimensional density map of frozen-hydrated, deglycosylated, human erythrocyte AQP1, viewed approximately perpendicular to the bilayer, showing one monomer and portions of adjacent monomers within a tetramer.
Figure 2: Intra- and inter-monomer interactions.
Figure 3: Demonstration of the in-plane pseudo-2-fold symmetry in the AQP1 monomer.
Figure 4: A surface-shaded representation showing an example of bridging density that suggests linkages of the central block (asterisk) to helices D and F.

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Acknowledgements

We thank V. Unger and R. Nunn for discussions; M. Pique for help in generating the stereograph; and R. Milligan, R. Nunn, V. Unger and M. Wiener for comments on the manuscript. This work was supported by grants from the NIH (A.K.M., A.S.V. and M.Y.), a grant-in-aid from the American Heart Association (A.K.M.) and the Donald E. and Delia B. Baxter Research Foundation (M.Y.). M.Y. is an established investigator of the American Heart Association and is supported by Bristol Myers-Squibb.

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Author notes

  1. A. N. van Hoek

    Present address: Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charleston, MA, 02129, USA

Authors and Affiliations

  1. *Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Anchi Cheng, A. N. van Hoek, M. Yeager & A. K. Mitra

  2. †Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, 94143, California, USA

    A. S. Verkman

  3. ‡Division of Cardiovascular Diseases, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, 92037, California, USA

    M. Yeager

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  1. Anchi Cheng
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Correspondence to A. K. Mitra.

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Cheng, A., van Hoek, A., Yeager, M. et al. Three-dimensional organization of a human water channel. Nature 387, 627–630 (1997). https://doi.org/10.1038/42517

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