Electron paramagnetic resonance spectroscopy on G-protein-coupled receptors: Adopting strategies from related model systems

Membrane proteins, including ion channels, transporters and G-protein-coupled receptors (GPCRs), play a significant role in various physiological processes. Many of these proteins are difficult to express in large quantities, imposing crucial experimental restrictions. Nevertheless, there is now a wide variety of studies available utilizing electron paramagnetic resonance (EPR) spectroscopic techniques that expand experimental accessibility by using relatively small quantities of protein. Here, we give an overview starting from basic strategies in EPR on membrane proteins with a focus on GPCRs, while emphasizing several applications from recent years. We highlight how the arsenal of EPR-based techniques may provide significant further contributions to understanding the complex molecular machinery and energetic phenomena responsible for seamless workflow in essential biological processes.