A farnesylated domain in the G protein γ subunit is a specific determinant of receptor coupling

Oleg G. Kisselev, Marina V. Ermolaeva, Narasimhan Gautam

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

The interaction between receptor and a heterotrimeric G protein (αβγ) 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 γ subunit of the G protein, G(t), directly stabilizes the active form of rhodopsin, metarhodopsin II (M II), and also uncouples rhodopsin-G(t) 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 γ subunit tail are specific determinants of receptor-G protein interaction. These results also suggest a general function for the family of G protein γ subunits in signaling.

Original languageEnglish
Pages (from-to)21399-21402
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number34
StatePublished - Aug 26 1994

Fingerprint

Dive into the research topics of 'A farnesylated domain in the G protein γ subunit is a specific determinant of receptor coupling'. Together they form a unique fingerprint.

Cite this