title: Serine 171, a conserved residue in the gamma-aminobutyric acid type A (GABAA) receptor gamma2 subunit, mediates subunit interaction and cell surface localization.
abstract: Serine 171 in the GABA(A) receptor gamma2 subunit is highly conserved in the ligand-gated ion channel superfamily. In this paper, we report that mutating serine 171 within gamma2 to glycine or cysteine prevents the interaction of gamma2 with alpha2 and beta1 when these subunits are co-expressed in human embryo kidney 293 cells, resulting in intracellular retention of gamma2. Structure analysis based on a three-dimensional homology model of gamma2 (Ernst, M., Brauchart, D., Boresch, S., and Sieghart, W. (2003) Neuroscience 119, 933-943) reveals that serine 171 may play a critical role in the formation and stabilization of an exposed turn structure that is part of the subunit interaction site. Mutation of serine 171 in the gamma2 subunit could therefore result in alteration of the structure of the subunit interaction site, preventing correct subunit assembly.
authors.affiliation: Incyte Corporation, Palo Alto, California 94304, USA. pjin@incyte.com
authors.forename: Pei
authors.initials: P
authors.lastname: Jin
authors.forename: Dirk
authors.initials: D
authors.lastname: Walther
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Courtney
authors.initials: C
authors.lastname: Rowe-Teeter
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Fu
mesh_terms: D000595:Amino Acid Sequence; D001569:Benzodiazepines / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D006801:Humans; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: C546279:GABRG2 protein, human; D008024:Ligands; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D012694:Serine