Activation of G-protein-coupled receptors by hydration driven sponge mechanism

G-protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human genome and act as signal transducers that enable transmembrane communication between cells and membrane-bound organelles. Despite many GPCR structures having water molecules within their transmembrane regions, the role that solvent molecules play in the receptor dynamics and signaling behavior remains unexplored. Here we show experimentally that activation of the archetypical GPCR rhodopsin in the lipid membrane is slaved to bulk water movements into the protein.