Structural highlights
Function
[GLRA3_HUMAN] The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Publication Abstract from PubMed
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 A X-ray structure of the human glycine receptor-alpha3 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.
Crystal structure of human glycine receptor-alpha3 bound to antagonist strychnine.,Huang X, Chen H, Michelsen K, Schneider S, Shaffer PL Nature. 2015 Oct 8;526(7572):277-80. doi: 10.1038/nature14972. Epub 2015 Sep 28. PMID:26416729[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang X, Chen H, Michelsen K, Schneider S, Shaffer PL. Crystal structure of human glycine receptor-alpha3 bound to antagonist strychnine. Nature. 2015 Oct 8;526(7572):277-80. doi: 10.1038/nature14972. Epub 2015 Sep 28. PMID:26416729 doi:http://dx.doi.org/10.1038/nature14972
