Structural Findings Reveal How Distinct GPCR Ligands Create Different Levels of Activation

Structural findings reveal how distinct GPCR ligands create different levels of activation

G-protein coupled receptors (GPCRs) are proteins triggered by ligands (protein-binding chemicals) from outside cells to transmit signals inside the cell. These signals are transmitted primarily through the activation of G proteins, which produce various physiological effects.

Non-equilibrium snapshots of ligand efficacy at the μ-opioid receptor

Distinct ligands for the same G-protein coupled receptor (GPCR) activate intracellular signaling partners to varying extents, but the molecular mechanisms driving these differences remain elusive. Hypothesizing that such differences in signaling efficacy may be captured structurally in intermediate states under non-equilibrium conditions, we implemented a time-resolved (TR) cryo-EM approach to visualize the GTP-induced activation of the Gαiβγ he…