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

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.

[1]  M. Borgnia,et al.  Reconstitution and functional comparison of purified GlpF and AqpZ, the glycerol and water channels from Escherichia coli , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A Cheng,et al.  Visualization of a water-selective pore by electron crystallography in vitreous ice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D C Rees,et al.  Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. , 1998, Science.

[4]  B. Roux,et al.  Free energy profiles for H+ conduction along hydrogen-bonded chains of water molecules. , 1998, Biophysical journal.

[5]  P. Agre,et al.  Aquaporin CHIP: the archetypal molecular water channel. , 1993, The American journal of physiology.

[6]  P. Agre,et al.  Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. , 1988, The Journal of biological chemistry.

[7]  T. Zeuthen,et al.  Transport of Water and Glycerol in Aquaporin 3 Is Gated by H+ * , 1999, The Journal of Biological Chemistry.

[8]  T. Zeuthen,et al.  Bidirectional Water Fluxes and Specificity for Small Hydrophilic Molecules in Aquaporins 0–5* , 1998, The Journal of Biological Chemistry.

[9]  F. Marumo,et al.  Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol. , 1998, Biochemical and biophysical research communications.

[10]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[11]  R. Huber,et al.  The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Verkman.  Water channels in cell membranes. , 1992, Annual review of physiology.

[13]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[14]  U. Singh,et al.  A NEW FORCE FIELD FOR MOLECULAR MECHANICAL SIMULATION OF NUCLEIC ACIDS AND PROTEINS , 1984 .

[15]  J. H. Park,et al.  Phylogenetic Characterization of the MIP Family of Transmembrane Channel Proteins , 1996, The Journal of Membrane Biology.

[16]  A. Cheng,et al.  Three-dimensional organization of a human water channel , 1997, Nature.

[17]  B. Wallace,et al.  The pore dimensions of gramicidin A. , 1993, Biophysical journal.

[18]  R. Bartucci,et al.  Sterically stabilized liposomes of DPPC/DPPE-PEG:2000. A spin label ESR and spectrophotometric study. , 1998, Biophysical chemistry.

[19]  E A Merritt,et al.  Raster3D: photorealistic molecular graphics. , 1997, Methods in enzymology.

[20]  N. Agmon,et al.  The Grotthuss mechanism , 1995 .

[21]  G. Bricogne,et al.  [27] Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. , 1997, Methods in enzymology.

[22]  D. Fu,et al.  Structure of a glycerol-conducting channel and the basis for its selectivity. , 2000, Science.

[23]  Andreas Engel,et al.  Structural determinants of water permeation through aquaporin-1 , 2000, Nature.

[24]  B. Jap,et al.  Crystallization and preliminary X-ray crystallographic analysis of water channel AQP1. , 2000, Acta crystallographica. Section D, Biological crystallography.

[25]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[26]  P. Agre,et al.  Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[28]  Huilin Li,et al.  Molecular design of aquaporin-1 water channel as revealed by electron crystallography , 1997, Nature Structural Biology.

[29]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[30]  P. Agre,et al.  Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. , 1991, The Journal of biological chemistry.

[31]  P. Agre,et al.  Ultrastructure, pharmacologic inhibition, and transport selectivity of aquaporin channel-forming integral protein in proteoliposomes. , 1994, Biochemistry.

[32]  Z. Otwinowski,et al.  Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[33]  B. Jap,et al.  Structure of the osmo-regulated H2O-channel, AQP-CHIP, in projection at 3.5 A resolution. , 1995, Journal of molecular biology.

[34]  Ponamarev Mv,et al.  Perturbation of the internal water chain in cytochrome f of oxygenic photosynthesis: loss of the concerted reduction of cytochromes f and b6. , 1998 .

[35]  A Cheng,et al.  Three-dimensional fold of the human AQP1 water channel determined at 4 A resolution by electron crystallography of two-dimensional crystals embedded in ice. , 2000, Journal of molecular biology.

[36]  M. Borgnia,et al.  Cellular and molecular biology of the aquaporin water channels. , 1999, Annual review of biochemistry.

[37]  H. Michel,et al.  Interruption of the water chain in the reaction center from Rhodobacter sphaeroides reduces the rates of the proton uptake and of the second electron transfer to QB. , 1995, Biochemistry.

[38]  Andreas Engel,et al.  The three-dimensional structure of aquaporin-1 , 1997, Nature.

[39]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.