PROGRESS ON THE STRUCTURE AND FUNCTION OF AQUAPORIN-1

Life exists in water as universal solvent, and cells need to deal with its influx and efflux. Nature has accomplished the almost impossible, creating:membrane channels with both a high flux and a high specifici ty for water The first water channel was discovered in red blood cell membranes. Today known as aquaporin-1, this channel was found to be cl osely related to the major integral protein (MIP)(1) of the eye lens. Cloning and sequencing of numerous related proteins of the MIP family revealed the widespread occurrence of such channels, suggesting an ess ential physiological function. Their structures hold the clues to the remarkable water channel activity, as well as to the arrangement of tr ansmembrane segments in general. Recent medium resolution three-dimens ional electron microscopic studies determined a tetrameric complex wit h six tilted transmembrane helices per monomer. The helices within eac h monomer surround a central density formed by two interhelical loops implicated by mutagenesis in the water channel function. A combination of sequence analysis and assignment of the observed densities to pred icted helices provides a basis For speculation on the nature of the wa ter course through the protein. In particular, four highly conserved. polar residues, E142-N192-N76-E17, are proposed to form a chain of key groups involved in the pathway of water how through the channel. (C) 1998 Academic Press.