GEC1-κ Opioid Receptor Binding Involves Hydrophobic Interactions

被引:17
作者
Chen, Yong [1 ]
Chen, Chongguang
Kotsikorou, Evangelia [2 ]
Lynch, Diane L. [2 ]
Reggio, Patricia H. [2 ]
Liu-Chen, Lee-Yuan [1 ]
机构
[1] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA
[2] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27402 USA
基金
美国国家卫生研究院;
关键词
MEMBRANE-TRANSPORT MODULATOR; PROTEIN GABARAP; CRYSTAL-STRUCTURE; GABA(A)-RECEPTOR-ASSOCIATED PROTEIN; CONFORMATIONAL MEMORIES; GABA(A) RECEPTORS; DOWN-REGULATION; MESSENGER-RNAS; IDENTIFICATION; EXPRESSION;
D O I
10.1074/jbc.M808303200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We demonstrated previously that the protein GEC1 (glandular epithelial cell 1) bound to the human kappa opioid receptor (hKOPR) and promoted cell surface expression of the receptor by facilitating its trafficking along the secretory pathway. Here we showed that three hKOPR residues (Phe(345), Pro(346), and Met(350)) and seven GEC1 residues (Tyr(49), Val(51), Leu(55), Thr(56), Val(57), Phe(60), and Ile(64)) are indispensable for the interaction. Modeling studies revealed that the interaction was mediated via direct contacts between the kinked hydrophobic fragment in hKOPR C-tail and the curved hydrophobic surface in GEC1 around the S2 beta-strand. Intramolecular Leu(44)-Tyr(109) interaction in GEC1 was important, likely by maintaining its structural integrity. Microtubule binding mediated by the GEC1 N-terminal domain was essential for the GEC1 effect. Expression of GEC1 also increased cell surface levels of the GluR1 subunit and the prostaglandin EP3.f receptor, which have FPXXM and FPXM sequences, respectively. With its widespread distribution in the nervous system and its predominantly hydrophobic interactions, GEC1 may have chaperone-like effects for many cell surface proteins along the biosynthesis pathway.
引用
收藏
页码:1673 / 1685
页数:13
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