In vertebrates, GABAA receptors mediate both phasic and tonic neuronal inhibition in the adult central nervous system. Their dysfunction leads to channelopathies associated with epilepsy, insomnia, anxiety and chronic pain. GABAA receptors are among the most important human drug targets owing to their many allosteric sites, which bind compounds with anticonvulsant, anti-anxiety, analgesic, sedative and anaesthetic properties. Some of these—such as benzodiazepines (BZDs), which are typically positive allosteric modulators—entered clinical use decades before the identity of their receptors was known. This structure is part of an amazing study by Masiulis et al (Nature 565, 454–459, 2019), reporting a series of high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABAA receptor in lipid nanodiscs, complexed with several drugs. Here you can the structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with diazepam, in yellow spheres (PDB code: 6HUP)

#molecularart ... #gaba ... #receptor ... #pain ... #diazepam ... #anxiety ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint