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Updated: Dec 5, 2025

Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors GPCRs
Published on: February 5, 2022
A method for identifying G protein-coupled receptor dimers and their interfaces
Jing Chen1, Xin Cai2, Maocai Yan3
1Neurobiology Key Laboratory of Jining Medical University, Jining 272067, China; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Abstract:
The G protein-coupled receptor (GPCR) dimer interface plays an important role in the formation and stabilization of the dimer. Therefore, identifying the potential receptor-receptor interface is an important part of studying GPCRs. Various strategies have been employed to study the GPCR dimer interface and explore its functional significance, but experimental methods lack robustness and calculations are laborious. Herein, we report a combined optimized experimental and calculation approach for identifying and structurally characterizing GPCR dimer interfaces, and constructing atomic resolution models. Using a transmembrane domain (TM) peptide containing a human immunodeficiency virus trans-acting transcriptional activator (HIV-TAT) protein transduction motif, matrix-assisted laser desorption tandem time-of-flight mass spectrometry (MALDITOF-MS), and bioluminescence resonance energy transfer (BRET), we successfully identified Apelin receptor (APJ)/Nociceptin receptor 1 (ORL1) and APJ/Vasopressin receptor 2 (V2R) heterodimer interfaces, and two key sites mediating dimerization. This method can identify dimer interfaces of GPCR homodimers and heterodimers.
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