NMR structure of an intracellular third loop peptide of human GABA(B) receptor |
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Authors: | Kikkou Tatsuhiko Matsumoto Osamu Ohkubo Tadayasu Kobayashi Yuji Tsujimoto Gozoh |
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Affiliation: | a Faculty of Pharmaceutical Sciences, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan b Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan c Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan |
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Abstract: | GABAB receptor is a G protein-coupled receptor for GABA and drug target for neurological and psychiatric disorders. From the analysis of GTPγS binding assay, we found that a synthesized peptide (GABAb: ETKSVSTEKINDHR) corresponding to the intracellular third loop region of metabotropic GABAB receptor could activate Gi protein α subunit directly. The three dimensional molecular structure of the peptide in SDS-d25 micelles was determined by 2D 1H-NMR spectroscopy. GABAb peptide formed an α helical structure and a positive charge cluster at the C-terminal site. These structural features were also found in several other G protein activating peptides. From the comparison among these peptides, we found that peptides with high helical content show the high activity. |
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Keywords: | COSY, correlated spectroscopy G protein, guanine nucleotide-binding protein GABA, γ-amino-butyric acid NOE, nuclear overhauser effect, also used for NOESY cross peak NOESY, NOE spectroscopy ppm, parts per million SDS-d25, sodium dodecyl-d25 sulfate |
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