Identification of the amino acid residues involved in selective agonist binding in the first extracellular loop of the δ‐ and μ‐opioid receptors

FEBS Letters

Terasako, Kiyoshi¹  Kato, Shigeshisa¹  Fukuda, Kazuhiko¹  Mori, Kenjiro¹ 

[1] Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-01, Japan

关键词: Opioid receptor;    Site-directed mutagenesis;    cDNA expression;    Agonist-binding affinity;    G-proteins;    guanine nucleotide-binding regulatory proteins;    DPDPE;    [d-penicillamine2;    d-penicillamine5]enkephaline;    DAGO;    [d-Ala2;    MePhe4;    Gly-ol5]enk ephalin;    ICL;    intracellular loop;    TM;    transmembrane segment;    ECL;    extracellular loop;    EKC;    ethylketocyclazocine;   

DOI  :  10.1016/0014-5793(95)01034-C

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Effects of amino acid substitutions in the first extracellular loop region of the β- and μ-opioid receptors were examined. Substitution of lysine-108 of the δ-receptor (δK108) with asparagine improved affinity to [d-Ala²,MePhe⁴,Gly-ol⁵]enk ephalin (DAGO), a μ-selective peptide agonist, to be comparable with that of the μ-receptor. On the other hand, replacement of mN127 with lysine decreased the affinity to DAGO by ∼ 15-fold. These results suggest that dK108 and mN127, which correspond to each other in the aligned amino acid sequences, mainly determine the difference in DAGO binding affinity between the δ- and μ-receptors.

【 授权许可】

Unknown