Molecular determinants for G protein betagamma modulation of ionotropic glycine receptors
| Autor: | Svenja Haeger, Günther Schmalzing, Gustavo Moraga-Cid, Luis G. Aguayo, Laerte Oliveira, Leonardo Guzmán, Juan Olate, Gonzalo E. Yévenes |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular G protein Protein subunit Amino Acid Motifs Lipid Bilayers Molecular Sequence Data Biology Biochemistry Protein Structure Secondary Cell Line Receptors Glycine GTP-Binding Proteins GTP-Binding Protein gamma Subunits Humans Amino Acid Sequence Receptor Molecular Biology Glycine receptor Ion channel GTP-Binding Protein beta Subunits Cell Biology Cell biology Electrophysiology Transmembrane domain Nicotinic acetylcholine receptor Intracellular Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 281(51) |
| ISSN: | 0021-9258 |
| Popis: | The ligand-gated ion channel superfamily plays a critical role in neuronal excitability. The functions of glycine receptor (GlyR) and nicotinic acetylcholine receptor are modulated by G protein betagamma subunits. The molecular determinants for this functional modulation, however, are still unknown. Studying mutant receptors, we identified two basic amino acid motifs within the large intracellular loop of the GlyR alpha(1) subunit that are critical for binding and functional modulation by Gbetagamma. Mutations within these sequences demonstrated that all of the residues detected are important for Gbetagamma modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are alpha-helixes near transmembrane domains 3 and 4, near to the lipid bilayer and highly electropositive. Our results demonstrate for the first time the sites for G protein betagamma subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling. |
| Databáze: | OpenAIRE |
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