Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers

Abstract Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout nervous system. They have been shown to be modulated by lipid environment, however underlying mechanism is not well understood. We report three structures 5-HT 3A serotonin (5HT 3 R) reconstituted into saposin-based bilayer discs: a symmetric and an asymmetric apo state, agonist-bound state. In comparison previously published 5HT R conformations detergent, stabilises more tightly packed, ‘coupled’ involving cluster highly conserved residues. consequence, conformation adopts wide-open pore capable conducting sodium ions unbiased molecular dynamics (MD) simulations. Taken together, we provide structural basis for modulation membrane model activation receptor.