Illuminating the Path to Target GPCR Structures and Functions

Abstract

G-Protein-coupled receptors (GPCRs) are ubiquitous within eukaryotes, responsible for a wide array of physiological and pathological processes. Indeed, the fact that they are the most drugged target in the human genome is indicative of their importance. Despite the clear interest in GPCRs, most information regarding their activity has been so far obtained by analyzing the response from a “bulk medium”. As such, this Perspective summarizes some of the common methods for this indirect observation. Nonetheless, by inspecting approaches applying super-resolution imaging, we argue that imaging is perfectly situated to obtain more detailed structural and spatial information, assisting in the development of new GPCR-targeted drugs and clinical strategies. The benefits of direct optical visualization of GPCRs are analyzed in the context of potential future directions in the field.

Illuminating the structural basis of human neurokinin 1 receptor (NK1R) antagonism through classical all‐atoms molecular dynamics simulations

“…G‐protein coupled receptors (GPCRs) are seven transmembrane (TM) proteins that bestride the cell membrane and modulate intracellular effectors in response to the extracellular stimuli 1 tantamount to biogenic amines, hormones, peptides, neurotransmitters, ions, odorants, and photons to transduce a multitude of physiological processes along with cell metabolism, growth, neurotransmission and sensory perception 2 . Studies have remarked the use of GPCRs as successful drug target class for their wide range of classifications, subtypes and isoforms, as well as their notable contribution in signalling pathways akin to various diseases, including endocrinological disorders, 3,4 viral infections, 5,6 immunological disorders, 7 cardiovascular, 7,8 sense disorders, 9 inflammatory, 10,11 and cancer 12 …”