Title: Multi-Site Binding Of A General Anesthetic To The Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC
Authors: Spurny, Radovan ×
Billen, Bert
Howard, Rebecca J
Brams, Marijke
Debaveye, Sarah
Price, Kerry L
Weston, David A
Strelkov, Sergei
Tytgat, Jan
Bertrand, Sonia
Bertrand, Daniel
Lummis, Sarah C R
Ulens, Chris #
Issue Date: Mar-2013
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:288 issue:12 pages:8355-8364
Abstract: Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABAA/C receptors and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anaesthetics. Here, we report the X-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore, and equates with a non-competitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7-β10 strands. Together, these results extend our understanding of pLGIC modulation, and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multi-site model of allosteric modulation in this family of ion channels.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Structural Neurobiology
× corresponding author
# (joint) last author

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