1. M. E. Mller-Institute for Microscopic Structural Biology at the Biozentrum, University of Basel, Basel CH-4056, Switzerland
2. International Institute for Advanced Research, Matsushita Electric Industrial Co., Ltd., 3-4 Hikaridai, Seika 619-02, Japan
3. Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-Ku, Kyoto, 606-01, Japan
4. Departments of Biological Chemistry and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA
5. Present address: Krebs Institute for Biomolecular Biology, Department of Molecular Biology and Biotechnology, University of Sheffield, PO Box 594, Sheffield S10 2UH, UK.

Correspondence to: Andreas Engel¹ Correspondence and requests for materials should be addressed to A.E.

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 channels^{4, 5, 6}. When reconstituted into lipid bilayers, the protein forms two-dimensional lattices with a unit cell containing two tetramers in opposite orientation^{7, 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 -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.