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Publication Abstract from PubMed

Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, gamma-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 anesthetics. 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 noncompetitive 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 beta7-beta10 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 multisite model of allosteric modulation in this family of ion channels.

Multisite Binding of a General Anesthetic to the Prokaryotic Pentameric Erwinia chrysanthemi Ligand-gated Ion Channel (ELIC).,Spurny R, Billen B, Howard RJ, Brams M, Debaveye S, Price KL, Weston DA, Strelkov SV, Tytgat J, Bertrand S, Bertrand D, Lummis SC, Ulens C J Biol Chem. 2013 Mar 22;288(12):8355-64. doi: 10.1074/jbc.M112.424507. Epub 2013, Jan 30. PMID:23364792^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.