title: The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins.
abstract: Receptors for the major excitatory neurotransmitter glutamate include metabotropic (G protein-coupled) and ionotropic (glutamate-gated ion channel) types. These receptors have large, presumably extracellular, amino-terminal domains. Sensitive sequence analysis techniques indicate that the metabotropic receptor extracellular domain is similar to bacterial periplasmic amino acid binding proteins. A structural model built using the observed similarity predicts a ligand-binding site, and mutants with conservative amino acid substitutions at this site are shown to have reduced ligand affinity. The metabotropic receptor extracellular domain is a member of a family of structural domains linked to a variety of receptor types, including ionotropic glutamate receptors.
authors.affiliation: ZymoGenetics, Inc., Seattle, Washington 98105.
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Hara
authors.forename: P O
authors.initials: PO
authors.lastname: Sheppard
authors.forename: H
authors.initials: H
authors.lastname: Thøgersen
authors.forename: D
authors.initials: D
authors.lastname: Venezia
authors.forename: B A
authors.initials: BA
authors.lastname: Haldeman
authors.forename: V
authors.initials: V
authors.lastname: McGrane
authors.forename: K M
authors.initials: KM
authors.lastname: Houamed
authors.forename: C
authors.initials: C
authors.lastname: Thomsen
authors.forename: T L
authors.initials: TL
authors.lastname: Gilbert
authors.forename: E R
authors.initials: ER
authors.lastname: Mulvihill
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016208:Databases, Factual; D005544:Forecasting; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008024:Ligands; D017470:Receptors, Glutamate