Protein–Protein Interactions of Odorant and G Protein-Coupled Receptors: A BRET Analysis Approach

Abstract

Odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are pivotal not only for olfactory detection in the nose but also for various biological functions in extra-nasal tissues. The functional characterization of ORs presents significant challenges, especially due to the difficulty of achieving their surface expression in in vitro systems. Research indicates that interactions between ORs and other receptors, as well as OR multimerization, are crucial for their membrane localization and the modulation of signaling pathways. Utilizing the bioluminescence resonance energy transfer (BRET) assay, a technique for investigating protein–protein interactions, our study quantifies the interactions between ORs and various receptors. This approach provides novel insights into OR molecular dynamics, emphasizing the role of OR multimerization. By exploring into these complexities, our work aims to enhance the understanding of cellular signaling mechanisms and promote the development of innovative therapeutic strategies. © The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 2025.