Structures and transitions of the serotonin 5-HT3 receptor
Invité par Jean-Louis BESSEREAU.
Résumé
The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel. It belongs to a large family of receptors that transduce signals across the plasma membrane: upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions, which result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression. I will present structures of the 5-HT3 receptor obtained by crystallography or cryo-electron microscopy. The structures, obtained in complex with inhibitors or agonists, represent snapshots in different states: inhibited, pre-active, active. Together with molecular dynamics simulations and functional recordings, they reveal the molecular mechanism of the fast neurotransmission mediated by 5HT3 receptors.