1. National Institute for Physiological Sciences, Okazaki 444-8585, Japan
2. Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan
3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115-5730, USA
4. Departments of Biological Chemistry and Medicine, Johns Hopkins University School of Medicine, Baltimore , Maryland 21205-2185, USA
5. M. E. Müller-Institute for Microscopy at the Biozentrum, University of Basel, Basel CH-4056 , Switzerland
6. These authors contributed equally to this work.

Correspondence to: Yoshinori Fujiyoshi³ Correspondence and requests for materials should be addressed to Y.F. (e-mail: Email: yoshi@em.biophys.kyoto-u.ac.jp). The coordinates of AQP1 reported in this paper have been deposited in the Protein Data Bank (Research Collaboratory for Structural Bioinformatics), PDB ID no. 1FQY.

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.