Direct Structural Insights into GABA Receptor Pharmacology.

GABA receptors are pentameric ligand-gated ion channels that mediate most fast neuronal inhibition in the brain. In addition to their important physiological roles, they are noteworthy in their rich pharmacology; prominent drugs used for anxiety, insomnia, and general anesthesia act through positive modulation of GABA receptors. Direct structural information for how these drugs work was absent until recently. Efforts in structural biology over the past few years have revealed how important drug classes and natural products interact with the GABA receptor, providing a foundation for studies in dynamics and structure-guided drug design. Here, we review recent developments in GABA receptor structural pharmacology, focusing on subunit assemblies of the receptor found at synapses.