New research reported in Current Opinion in Structural Biology combines structural and spectroscopic approaches to garner precise information on the functioning of GPCRs (G protein-coupled receptors). GPCRs are a large family of membrane receptors that share a common structure; they have been linked to neurodegenerative, cardiovascular diseases, and some cancers.
"Currently, scientists have two options when it comes to studying proteins,” explains Anastasia Gusach, a research fellow at the MIPT Laboratory of Structural Biology of G-protein Coupled Receptors, where the research was conducted. “They can either 'freeze' a protein and have its precise static snapshot, or study its dynamics at the cost of losing details. The former approach uses methods such as crystallography and cryogenic electron microscopy; the latter uses spectroscopic techniques.”
But, as Gusach elaborated, neither of these approaches provides all the information one would want when looking at GPCRs. So, MIPT biophysicists decided to combine the techniques in hopes of revealing both structural and dynamics information.
"Studying the GPCR dynamics uses cutting-edge methods of experimental biophysical analysis such as nuclear magnetic resonance (NMR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and advanced fluorescence microscopy techniques including single-molecule microscopy," says Alexey Mishin, deputy head of the MIPT Laboratory for Structural Biology of G-protein Coupled Receptors.
GPCRs are a target for many drugs because the membrane proteins have been connected to obesity, diabetes, and mental disorders, as well as the aforementioned diseases. The researchers hope that their technique will aid in developing more efficient drugs that target the GPCR family as well as provide insight on structure-based drug design overall.
"Biophysicists that use different methods to study GPCRs have been widely organizing collaborations that already bore some fruitful results. We hope that this review will help scientists specializing in different methods to find some new common ground and work together to obtain a better understanding of receptors' functioning," concludes Anastasia Gusach.