5CFB

Crystal Structure of Human Glycine Receptor alpha-3 Bound to Strychnine

Summary for 5CFB

• Entry DOI: 10.2210/pdb5cfb/pdb
• Descriptor: Glycine receptor subunit alpha-3,Glycine receptor subunit alpha-3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, STRYCHNINE, ... (4 entities in total)
• Functional Keywords: ligand-gated ion channel, neurotransmitter receptor, membrane protein, cys-loop receptor, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 5
• Total formula weight: 212471.50

Authors

Shaffer, P.L.,Huang, X.,Chen, H. (deposition date: 2015-07-08, release date: 2015-09-30, Last modification date: 2024-11-06)

Primary citation

Huang, X.,Chen, H.,Michelsen, K.,Schneider, S.,Shaffer, P.L.
Crystal structure of human glycine receptor-alpha 3 bound to antagonist strychnine.
Nature, 526:277-280, 2015

PubMed 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.

PubMed: 26416729
DOI: 10.1038/nature14972

Experimental method

X-RAY DIFFRACTION (3.04 Å)