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Structural basis of water-specific transport through the AQP1 water channel

Nature volume 414, pages 872–878 (2001)Cite this article

Abstract

Water channels facilitate the rapid transport of water across cell membranes in response to osmotic gradients. These channels are believed to be involved in many physiological processes that include renal water conservation, neuro-homeostasis, digestion, regulation of body temperature and reproduction. Members of the water channel superfamily have been found in a range of cell types from bacteria to human. In mammals, there are currently 10 families of water channels, referred to as aquaporins (AQP): AQP0–AQP9. Here we report the structure of the aquaporin 1 (AQP1) water channel to 2.2 Å resolution. The channel consists of three topological elements, an extracellular and a cytoplasmic vestibule connected by an extended narrow pore or selectivity filter. Within the selectivity filter, four bound waters are localized along three hydrophilic nodes, which punctuate an otherwise extremely hydrophobic pore segment. This unusual combination of a long hydrophobic pore and a minimal number of solute binding sites facilitates rapid water transport. Residues of the constriction region, in particular histidine 182, which is conserved among all known water-specific channels, are critical in establishing water specificity. Our analysis of the AQP1 pore also indicates that the transport of protons through this channel is highly energetically unfavourable.

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Figure 1: Models of AQP1, sequence alignment of selected superfamily members and a view of the density map.
Figure 2: Side-views of AQP1.
Figure 3: The effective pore diameter (a) and hydrophobicity (b) of the AQP1 and GlpF channels.
Figure 4: Selectivity filter water molecules and residues forming the hydrophilic face of the channel pore.
Figure 5: Residues defining the constriction region.

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Acknowledgements

Preliminary data collection and screening for heavy-atom derivatives were conducted at beamlines X25 at the National Synchrotron Light Source and 1–5 at Stanford Synchrotron Radiation Laboratory; data sets used in determining the model were collected at Beamline 5.0.2, Advanced Light Source, Lawrence Berkeley National Laboratory. We would like to thank all staff members of these beamlines for their assistance and B.-C. Wang for discussions on heavy-atom position refinement. This work is supported by funding from the National Institutes of Health and by the Office of Health and Environmental Research, US Department of Energy. The coordinates have been deposited in the Protein Data Bank under accession number 1J4N.

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Author notes

  1. Haixin Sui, Bong-Gyoon Han, John K. Lee and Bing K. Jap: These authors contributed equally to this work

Authors and Affiliations

  1. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, 94720, California, USA

    Haixin Sui, Bong-Gyoon Han, John K. Lee, Peter Walian & Bing K. Jap

  2. Graduate Group in Comparative Biochemistry, University of California, Berkeley, 94720, California, USA

    John K. Lee & Bing K. Jap

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  1. Haixin Sui
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Correspondence to Peter Walian or Bing K. Jap.

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Sui, H., Han, BG., Lee, J. et al. Structural basis of water-specific transport through the AQP1 water channel. Nature 414, 872–878 (2001). https://doi.org/10.1038/414872a

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