Amino acids 356-372 constitute a Gi-activator sequence of the alpha 2-adrenergic receptor and have a Phe substitute in the G protein-activator sequence motif.
The human alpha 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 alpha 2-F) was found to activate Gi and Go strongly with a saturated effect at 1-3 microM. Furthermore, the substitution of the C-terminal Phe of peptide alpha 2-F with Arg, Trp, and Tyr (but not Ala or Asp) did not appreciably affect the Gi-activating potency. It is suggested that the C-terminal basic residue of the B-B-X-X-B motif in Gi-activating sequences can be replaced by an aromatic residue.
Ikezu
T
T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Okamoto
T
T
Ogata
E
E
Nishimoto
I
I
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D010649:Phenylalanine; D011485:Protein Binding; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010649:Phenylalanine; D019204:GTP-Binding Proteins