title: Control of the Aquaporin-4 Channel Water Permeability by Structural Dynamics of Aromatic/Arginine Selectivity Filter Residues.
abstract: The aquaporins (AQPs) make up a family of integral membrane proteins that control cellular water flow. Gating of the water channel by conformational changes induced by phosphorylation or protein-protein interactions is an established regulatory mechanism for AQPs. Recent in silico and crystallographic analyses of the structural biology of AQPs suggest that the rate of water flow can also be controlled by small movements of single-amino acid side chains lining the water pore. Here we use measurements of the membrane water permeability of mammalian cells expressing AQP4 mutants to provide the first in vitro evidence in support of this hypothesis.
authors.affiliation: Molecular Organisation and Assembly in Cells Doctoral Training Centre, University of Warwick , Coventry CV4 7AL, U.K.
authors.forename: Philip
authors.initials: P
authors.lastname: Kitchen
authors.affiliation: Institute of Clinical Sciences, University of Birmingham , Edgbaston, Birmingham B15 2TT, U.K.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Conner
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D051401:Aquaporin 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000502:physiology*; D004285:Dogs; D005998:Glycine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008954:Models, Biological; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014867:Water / Q000378:metabolism*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D011993:Recombinant Fusion Proteins; D014867:Water; D006639:Histidine; D001120:Arginine; D005998:Glycine