Amino acids 356–372 constitute a G i-activator sequence of the α 2-adrenergic receptor and have a Phe substitute in the G protein-activator sequence motif

Abstract

The human α 2-adrenergic receptor contains the sequence KASRWRGRQNREKRFTF (amino acids 356–372) at the C-terminal end of its third intracellular loop. This sequence satisfies the structural criteria for G protein-activating sequences [(1992) J. Biol. Chem. 267, 8342–8346] except that the C-terminal sequence is B-B-X-X-Phe instead of B-B-X-B or B-B-X-X-B (B: basic residue, X: non-basic residue). Nevertheless, the synthetic peptide corresponding to this sequence (peptide α 2-F) was found to activate G i and G o strongly with a saturated effect at 1–3 μM. Furthermore, the substitution of the C-terminal Phe of peptide α 2-F with Arg, Trp, and Tyr (but not Ala or Asp) did not appreciably affect the G i-activating potency. It is suggested that the C-terminal basic residue of the B-B-X-X-B motif in G i-activating sequences can be replaced by an aromatic residue.