GABA receptor subunit M2-M3 linkers have asymmetric roles in pore gating and diazepam modulation.

GABA receptors (GABARs) are neurotransmitter-gated ion channels critical for inhibitory synaptic transmission as well as the molecular target for benzodiazepines (BZDs), one of the most widely prescribed class of psychotropic drugs today. Despite structural insight into the conformations underlying functional channel states, the detailed molecular interactions involved in conformational transitions and the physical basis for their modulation by BZDs are not fully understood. We previously identified that alanine substitution at the central residue in the α1 subunit M2-M3 linker (V279A) enhances the efficiency of linkage between the BZD site and the pore gate.