Amino acids 356–372 constitute a Gi‐activator sequence of the α2‐adrenergic receptor and have a Phe substitute in the G protein‐activator sequence motif

FEBS Letters

Nishimoto, Ikuo¹  Okamoto, Takashi¹  Ikezu, Tsuneya²  Ogata, Etsuro² 

[1] Cardiovascular Research Center, Harvard Medical School, Massachusetts General Hospital-East, 4th Floor, 149 13th Street, Charlestown, MA 02129, USA;Life Science Laboratory, Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan

关键词: α2-Adrenergic receptor;    Gi-coupling mechanism;    Gi-activator sequence;    G protein-activator sequence motif;    Aromatic amino acid;   

DOI  :  10.1016/0014-5793(92)81359-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human α₂-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 α₂-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 α₂-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.

【 授权许可】

Unknown