Main-chain hydrogen bonding in GABAA receptor gating and disease скачать в хорошем качестве

Main-chain hydrogen bonding in GABAA receptor gating and disease

Talk given by Marcel Goldschen-Ohm (University of Texas at Austin) as part of the International GCE Webinar series. Live talk given on November 20th, 2025. GABAA receptors are neurotransmitter-gated ion channels responsible for transducing most inhibitory synaptic signaling throughout the brain. Despite advances in resolving their 3-dimensional structure, we lack a comprehensive understanding for how several interfacial loops transduce the chemical energy from GABA binding in the extracellular domain to gating of the ion pore in the transmembrane domain. Here, I show that main-chain hydrogen bonding within and between these loops plays a previously unrecognized but essential role in this transduction, and its disruption is the atomic basis for several pathogenic variants in both GABAAand glycine receptors associated with epilepsy, developmental disability, or hyperekplexia.