How osmotic stress and crowding affect G-protein-coupled receptor activation

Abstract

G-protein-coupled receptors (GPCRs) are integral membrane proteins responsible for signal transduction across cellular membranes and constitute the largest class of medicinal targets. Although three-dimensional structures show the presence of structural water molecules within GPCRs, functional role of these water molecules has remained unknown. Our previous work has further shown a bulk influx of water stabilizing the active rhodopsin conformation [1]. Here we broadened the experimental approach to investigate how the conformational energetics of GPCR activation are modulated by water using a series of hydrophilic polymers including polyethylene glycols (PEGs), dextrans, polyvinylpyrrolidones, and their monomers.