Determination of the minimal functional ligand-binding domain of the GABAB1b receptor (2005)

Author(s): Deriu D, Gassmann M, Firbank S, Ristig D, Lampert C, Mosbacher J, Froestl W, Kaupmann K, Bettler B, Grutter MG

    Abstract: In the mammalian central nervous system, slow inhibitory neurotransmission is largely mediated by metabotropic GABA(B) receptors (where GABA stands for gamma-aminobutyric acid), which belong to the G-protein-coupled receptor gene family. Functional GABA(B) receptors are assembled from two subunits GABA(B1) (GABA(B) receptor subtype 1) and GABA(B2). For the GABA(B1) subunit, which binds the neurotransmitter GABA, two variants GABA(B1a) (GABA(B) receptor subtype 1 variant a) and GABA(B1b) have been identified. They differ at the very N-terminus of their large glycosylated ECD (extracellular domain). To simplify the structural characterization, we designed truncated GABA(B1) receptors to identify the minimal functional domain which still binds a competitive radioligand and leads to a functional, GABA-responding receptor when co-expressed with GABA(B2). We show that it is necessary to include all the portion of the ECD encoded by exon 6 to exon 14. Furthermore, we studied mutant GABA(B1b) receptors, in which single or all potential N-glycosylation sites are removed. The absence of oligosaccharides does not impair receptor function, suggesting that the unglycosylated ECD of GABA(B1) can be used for further functional or structural investigations.

    Notes: Journal Article

    Research Support, Non-U.S. Gov't


      • Date: 14-10-2004
      • Journal: Biochemical journal
      • Volume: 386
      • Issue: 3
      • Pages: 423-431
      • Publisher: Portland Press Ltd.
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Amino Acid Sequence


      Base Sequence

      Binding Sites

      Cell Line







      Models, Molecular

      Molecular Sequence Data

      Protein Structure, Quaternary

      Protein Structure, Tertiary


      Receptors, GABA-B/agonists/*chemistry/genetics/*metabolism

      Sequence Alignment

      Sequence Deletion/genetics

      Signal Transduction