Multiple GPCR Functional Assays Based on Resonance Energy Transfer Sensors

G protein-coupled receptors (GPCRs) represent one of the largest membrane protein families that participate in various physiological and pathological activities. Accumulating structural evidences have revealed how GPCR activation induces conformational changes to accommodate the downstream G protein or beta-arrestin. Multiple GPCR functional assays have been developed based on Forster resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) sensors to monitor the conformational changes in GPCRs, GPCR/G proteins, or GPCR/beta-arrestin, especially over the past two decades. Here, we will summarize how these sensors have been optimized to increase the sensitivity and compatibility for application in different GPCR classes using various labeling strategies, meanwhile provide multiple solutions in functional assays for high-throughput drug screening.

Automated summary

G protein-coupled receptors (GPCRs) are a large membrane protein family involved in physiological and pathological activities, and various sensors have been developed to monitor conformational changes for high-throughput drug screening purposes.