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Updated: Jul 18, 2026
06:45
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Transmembrane segment peptides can disrupt cholecystokinin receptor oligomerization without affecting receptor
Kaleeckal G Harikumar1, Maoqing Dong, Zhijie Cheng
1Cancer Center and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, Arizona 85259, USA.
Biochemistry
|December 6, 2006
Summary
The cholecystokinin (CCK) receptor
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- G protein-coupled receptor (GPCR) oligomerization is crucial for function.
- The molecular basis of cholecystokinin (CCK) receptor oligomerization remains unclear.
Purpose of the Study:
- To investigate the role of transmembrane (TM) segments in CCK receptor oligomerization.
- To identify specific TM domains involved in CCK receptor self-association.
Main Methods:
- Bioluminescence Resonance Energy Transfer (BRET) assays to quantify receptor oligomerization.
- Peptide competitive inhibition using synthetic TM peptides from the CCK receptor.
- Site-directed mutagenesis to probe specific TM faces.
Main Results:
- Transmembrane segments VI and VII of the CCK receptor were identified as key mediators of oligomerization.
- The lipid-exposed face of TM VI, specifically residues 317, 321, and 325, is critical for CCK receptor self-association.
- Disruption of CCK receptor oligomerization did not affect agonist binding, activity, or internalization.
Conclusions:
- CCK receptor oligomerization is primarily mediated by the external face of TM VI.
- This interaction supports an "external contact" dimerization model for CCK receptors.
- Oligomerization is not essential for CCK receptor signaling or trafficking.
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