title: Solution structure of the first intracellular loop of prostacyclin receptor and implication of its interaction with the C-terminal segment of G alpha s protein.
abstract: The amino acids (residues 39-51) responsible for the interaction between the first intracellular loop (iLP1) of the human prostacyclin receptor (IP) and G alpha s protein have been identified [Zhang, L., Huang, G., Wu, J., and Ruan, K. H. (2005) Biochemistry 44, 11389-11401]. To further characterize the structural/functional relationship of the iLP1 in coupling with the G alpha s protein, the solution structures of a constrained peptide (IP iLP1) that mimicked the iLP1 of the IP receptor in the absence and presence of a synthetic peptide, corresponding to the C-terminal 11 residues (Q384-L394 in the protein sequence) of the G alpha s protein (G alpha s-Ct), were determined by 2D 1H NMR spectroscopy. The NMR solution structural model of the iLP1 domain showed two turn structures in residues Arg41-Ala44 and Arg45-Phe49 with the conserved Arg45 at the center. The conformational change of the side chain of the Arg45 was observed upon the addition of the G alpha s-Ct peptide. On the other hand, the solution structural models of the G alpha s-Ct peptide in the absence and presence of the IP iLP1 peptide were also determined. The N-terminal domain (Q384-Q390 in the G alpha s protein) of the peptide adopted an alpha-helical conformation. However, the helical structure of the C-terminal domain (Q390-E392 in the G alpha s protein) of the peptide was destabilized upon addition of the IP iLP1 peptide. These structural studies have implied that there are direct or indirect contacts between the IP iLP1 domain and the C-terminal residues of the G alpha s protein in the receptor/G protein coupling. The possible charge and hydrophobic interactions between the two peptides were also discussed. These data prompted intriguing speculations on the IP/G alpha s coupling which mediates vasodilatation and inhibition of platelet aggregation.
authors.affiliation: Vascular Biology Research Center and Division of Hematology, Department of Internal Medicine, The University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Lihai
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.forename: Ke-He
authors.initials: KH
authors.lastname: Ruan
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D018360:Crystallography, X-Ray; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D044006:Receptors, Epoprostenol / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D044006:Receptors, Epoprostenol; D010649:Phenylalanine; D001120:Arginine; D019205:GTP-Binding Protein alpha Subunits, Gs; D000409:Alanine