title: Multiple modes for conferring surface expression of homomeric beta1 GABAA receptors.
abstract: The gamma-aminobutyric acid type A (GABA(A)) receptor assembles from individual subunits to form ligand-gated ion channels. Human (h) beta3 subunits assemble to form homomeric surface receptors in somatic cells, but hbeta1 subunits do not. We have identified three distinct sets of amino acid residues in the N-terminal extracellular domain of the hbeta1 subunit, which when mutated to the homologous residue in hbeta3 allow expression as a functional homomeric receptor. The three sets likely result in three modes of assembly. Mode 1 expression results from a single amino acid change at residue hbeta1 Asp-37. Mode 2 expression results from mutations of residues between positions 44 and 73 together with residues between positions 169 and 173. Finally, mode 3 results from the mutations A45V and K196R. Examination of homology-based structural models indicates that many of the residues are unlikely to be involved in physical inter-subunit interactions, suggesting that a major alteration is stabilization of an assembly competent form of the subunit. These mutations do not, however, have a major effect on the surface expression of heteromeric receptors which include the alpha1 subunit.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. john@morpheus.wustl.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Bracamontes
authors.forename: Joe Henry
authors.initials: JH
authors.lastname: Steinbach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D004594:Electrophysiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011784:Quail; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011963:Receptors, GABA-A; D001224:Aspartic Acid