Function of GB1 and GB2 subunits in G protein coupling of GABAB receptors
| Autor: | Lily Yeh Jan, Marta Margeta-Mitrovic, Yuh Nung Jan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
G protein
Recombinant Fusion Proteins Xenopus Models Neurological Molecular Sequence Data Class C GPCR Biology In Vitro Techniques Rhodopsin-like receptors GTP-Binding Proteins Heterotrimeric G protein Animals Amino Acid Sequence Receptor G protein-coupled receptor G protein-coupled receptor kinase Multidisciplinary Biological Sciences Cell biology Protein Structure Tertiary Protein Subunits Metabotropic receptor Biochemistry Receptors GABA-B Mutation Oocytes Female |
| Popis: | Many G protein-coupled receptors (GPCRs) have recently been shown to dimerize, and it was suggested that dimerization may be a prerequisite for G protein coupling. γ-aminobutyric acid type B (GABA B ) receptors (GPCRs for GABA, a major inhibitory neurotransmitter in the brain) are obligate heterodimers of homologous GB1 and GB2 subunits, neither of which is functional on its own. This feature of GABA B receptors allowed us to examine which of the eight intracellular segments of the heterodimeric receptor were important for G protein activation. Replacing any of the three intracellular loops of GB2 with their GB1 counterparts resulted in nonfunctional receptors. The deletion of the complete GB2 C terminus significantly attenuated the receptor function; however, the proximal 36 residues were sufficient for reconstitution of wild type-like receptor activity. In contrast, the GB1 C terminus could be deleted and GB1 intracellular loops replaced with their GB2 or mGluR1 equivalents without affecting the receptor function. In addition, a large portion of the GB1 i2 loop could be replaced with a random coil peptide without any functional consequences. Thus, GB2 intracellular segments are solely responsible for specific coupling of GABA B receptors to their physiologic effectors, G i and G protein-activated K + channels. These findings strongly support a model in which a single GPCR monomer is sufficient for all of the specific G protein contacts. |
| Databáze: | OpenAIRE |
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