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Inner leaflet intersubunit binding site in pLGICs. (A) GLIC-α1GABAAR chimera at pH 4.5 with THDOC (pdb 5osb). Q264 forms a hydrogen bond interaction with the 3-hydroxyl group of the neurosteroid, and W245 forms a hydrophobic ring stacking interaction with the steroid backbone. (B) Apo ELIC with phosphatidylethanolamine (pdb 6hjx). Shown is W224, which is a highly conserved tryptophan in pLGICs that interacts with neurosteroids (A) and forms this lipid binding site.
