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Updated: Feb 4, 2026

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
Published on: November 30, 2018
Structural basis of neurosteroid anesthetic action on GABAA receptors
Qiang Chen1, Marta M Wells1,2, Palaniappa Arjunan1,3
1Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Abstract:
Type A γ-aminobutyric acid receptors (GABAARs) are inhibitory pentameric ligand-gated ion channels in the brain. Many anesthetics and neurosteroids act through binding to the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood and no resting-state GABAAR structure has been determined. Here, we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-bound desensitized chimeric α1GABAAR (ELIC-α1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone binding to an inter-subunit TMD site. These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the channel gate in the pore-lining TM2 through the TM1-TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential.
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