Quantitative Insights into G Protein Signaling: A Review of Recent SPR Methodologies and Discoveries

G protein-coupled receptors (GPCRs), one of the largest and most versatile protein families, play a central role in transducing extracellular signals into intracellular responses and represent a significant class of therapeutic targets, especially in oncology. Aberrant GPCR signaling is increasingly recognized as a hallmark of various cancers, highlighting the urgent need for precise tools to decode their signaling dynamics. Surface Plasmon Resonance (SPR) biosensor technology has emerged as a powerful, label-free, real-time method to investigate these dynamic biomolecular interactions quantitatively. This review focuses on the significant contributions and advancements in applying SPR to G protein signaling research. We discuss SPR methodologies tailored for studying GPCRs and G proteins, including innovative immobilization strategies and analytical approaches. Key applications are highlighted, such as the characterization of ligand-GPCR binding kinetics, GPCR-G protein coupling and nucleotide exchange dynamics, interactions between G protein subunits and their effectors, and the elucidation of biased agonism. Furthermore, we examine the synergistic integration of SPR with complementary techniques such as cryo-electron microscopy and computational modeling, offering a multidimensional approach to understanding GPCR signaling. By illuminating the molecular intricacies underpinning GPCR-mediated pathways, SPR is advancing our mechanistic insights and catalyzing the development of next-generation therapeutics. This review underscores the transformative impact of SPR in GPCR research and its pivotal role in driving innovation in targeted therapy and precision medicine.

Keywords:

G Protein-Coupled Receptors (GPCRs) , Signal Transduction , Surface Plasmon Resonance (SPR) , Biomolecular Interactions , drug delivery