title: Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.
abstract: Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.
authors.affiliation: Department of Chemistry, Biochemistry and Biophysics, University of Gothenburg, Göteborg, Sweden.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fischer
authors.forename: Urszula
authors.initials: U
authors.lastname: Kosinska-Eriksson
authors.forename: Camilo
authors.initials: C
authors.lastname: Aponte-Santamaría
authors.forename: Madelene
authors.initials: M
authors.lastname: Palmgren
authors.forename: Cecilia
authors.initials: C
authors.lastname: Geijer
authors.forename: Kristina
authors.initials: K
authors.lastname: Hedfalk
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohmann
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
authors.forename: Richard
authors.initials: R
authors.lastname: Neutze
authors.forename: Karin
authors.initials: K
authors.lastname: Lindkvist-Petersson
mesh_terms: D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005615:Freezing; D015640:Ion Channel Gating; D050296:Microbial Viability; D008958:Models, Molecular; D010766:Phosphorylation; D010843:Pichia / Q000737:chemistry*; D017433:Protein Structure, Secondary; D018724:Spinacia oleracea / Q000737:chemistry; D040681:Structural Homology, Protein; D014443:Tyrosine / Q000378:metabolism; D014867:Water
chemical_list: D020346:Aquaporins; D014867:Water; D014443:Tyrosine