title: A farnesylated domain in the G protein gamma subunit is a specific determinant of receptor coupling.
abstract: The interaction between receptor and a heterotrimeric G protein (alpha beta gamma) is thought to involve the intracellular loops of receptors and specific domains on the G protein. Here we show that a chemically farnesylated peptide (P5far) specific to the carboxyl-terminal domain (amino acids 60-71: DKNPFKELKGGC) of the gamma subunit of the G protein, Gt, directly stabilizes the active form of rhodopsin, metarhodopsin II (M II), and also uncouples rhodopsin-Gt interaction. Peptide activity is significantly affected by the absence of the isoprenoid moiety. Moreover, we show that altering the amino acid sequence of the farnesylated peptide by randomizing the sequence, substituting hydrophobic with hydrophilic residues (F64T; L67S) or deleting amino acids 60-66 significantly reduces the ability of the peptide to stabilize M II. This indicates that both the farnesyl moiety and the structure of the gamma subunit tail are specific determinants of receptor-G protein interaction. These results also suggest a general function for the family of G protein gamma subunits in signaling.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: O G
authors.initials: OG
authors.lastname: Kisselev
authors.forename: M V
authors.initials: MV
authors.lastname: Ermolaeva
authors.forename: N
authors.initials: N
authors.lastname: Gautam
mesh_terms: D000595:Amino Acid Sequence; D005204:Farnesol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017368:Protein Prenylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013053:Spectrophotometry
chemical_list: D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D005204:Farnesol; D012243:Rhodopsin; D019204:GTP-Binding Proteins