Title : Crystal structure of human
glycine receptor-α3 bound to antagonist strychnine
Abstract :
- Neurotransmitter-gated ion channels of the Cys-loop receptor family are essential mediators of fast neurotransmission throughout the nervous system and are implicated in many neurological disorders
- Available X-ray structures of prokaryotic and eukaryotic Cys-loop receptors provide tremendous insights into the binding of agonists, the subsequent opening of the ion channel , and the mechanism of channel activation
- Yet the mechanism of inactivation by antagonists remains unknown
- Here we present a 3.0 Å X-ray structure of the human glycine receptor-α3 homopentamer in complex with a high affinity, high-specificity antagonist, strychnine
- Our structure allows us to explore in detail the molecular recognition of antagonists
- Comparisons with previous structures reveal a mechanism for antagonist-induced inactivation of Cys-loop receptors , involving an expansion of the orthosteric binding site in the extracellular domain that is coupled to closure of the ion pore in the transmembrane domain