NMR structure of an intracellular third loop peptide of human GABA(B) receptor.
GABA(B) receptor is a G protein-coupled receptor for GABA and drug target for neurological and psychiatric disorders. From the analysis of GTPgammaS binding assay, we found that a synthesized peptide (GABAb: ETKSVSTEKINDHR) corresponding to the intracellular third loop region of metabotropic GABA(B) receptor could activate G(i) protein alpha subunit directly. The three dimensional molecular structure of the peptide in SDS-d(25) micelles was determined by 2D (1)H-NMR spectroscopy. GABAb peptide formed an alpha 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.
Kikkou
Tatsuhiko
T
Faculty of Pharmaceutical Sciences, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
Matsumoto
Osamu
O
Ohkubo
Tadayasu
T
Kobayashi
Yuji
Y
Tsujimoto
Gozoh
G
D003198:Computer Simulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D018080:Receptors, GABA-B / Q000737:chemistry* / Q000648:ultrastructure*
D018080:Receptors, GABA-B