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Published on: June 9, 2017
GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect
Yong Chen1, Chongguang Chen, Evangelia Kotsikorou
1Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
The Journal of Biological Chemistry
|November 13, 2008
Summary
Glandular epithelial cell 1 (GEC1) protein interacts with the human kappa opioid receptor (hKOPR), enhancing its cell surface expression. This interaction involves specific amino acid residues and GEC1
Area of Science:
- Molecular biology
- Cell biology
- Neuroscience
Background:
- The protein GEC1 (glandular epithelial cell 1) was previously shown to bind the human kappa opioid receptor (hKOPR).
- GEC1 facilitates hKOPR trafficking along the secretory pathway, promoting cell surface expression.
Purpose of the Study:
- To identify the specific amino acid residues involved in the GEC1-hKOPR interaction.
- To elucidate the structural basis and mechanism of GEC1-mediated hKOPR cell surface expression.
Main Methods:
- Site-directed mutagenesis to identify indispensable residues in hKOPR and GEC1.
- Molecular modeling to visualize the interaction interface.
- Analysis of GEC1's effect on other cell surface proteins (GluR1, EP3.f receptor).
Main Results:
- Three hKOPR residues (Phe345, Pro346, Met350) and seven GEC1 residues (Tyr49, Val51, Leu55, Thr56, Val57, Phe60, Ile64) are critical for binding.
- Molecular modeling indicated hydrophobic interactions between hKOPR C-tail and GEC1's S2 beta-strand.
- GEC1's N-terminal domain binding to microtubules is essential for its function.
- GEC1 also increased cell surface levels of GluR1 and prostaglandin EP3.f receptor.
Conclusions:
- GEC1 utilizes specific hydrophobic interactions and microtubule binding to enhance cell surface expression of hKOPR.
- GEC1 may act as a chaperone for various cell surface proteins with similar sequence motifs (FPXXM/FPXM).
- These findings suggest a broader role for GEC1 in protein trafficking and cell surface expression within the nervous system.
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