title: Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z.
abstract: Aquaporins are a family of water and small molecule channels found in organisms ranging from bacteria to animals. One of these channels, the E. coli protein aquaporin Z (AqpZ), has been shown to selectively conduct only water at high rates. We have expressed, purified, crystallized, and solved the X-ray structure of AqpZ. The 2.5 A resolution structure of AqpZ suggests aquaporin selectivity results both from a steric mechanism due to pore size and from specific amino acid substitutions that regulate the preference for a hydrophobic or hydrophilic substrate. This structure provides direct evidence on the molecular mechanisms of specificity between water and glycerol in this family of channels from a single species. It is to our knowledge the first atomic resolution structure of a recombinant aquaporin and so provides a platform for combined genetic, mutational, functional, and structural determinations of the mechanisms of aquaporins and, more generally, the assembly of multimeric membrane proteins.
authors.affiliation: Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Savage
authors.forename: Pascal F
authors.initials: PF
authors.lastname: Egea
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Robles-Colmenares
authors.forename: Joseph D
authors.initials: JD
authors.lastname: O'Connell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
mesh_terms: D000595:Amino Acid Sequence; D020346:Aquaporins / Q000737:chemistry* / Q000302:isolation & purification; D002244:Carbon / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D003902:Detergents / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000302:isolation & purification; D005990:Glycerol / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000302:isolation & purification; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010100:Oxygen / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry
chemical_list: D020346:Aquaporins; D003902:Detergents; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C106425:aqpZ protein, E coli; D014867:Water; D002244:Carbon; D006859:Hydrogen; D005990:Glycerol; D010100:Oxygen