3ri5
C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab, ivermectin and picrotoxinC. elegans glutamate-gated chloride channel (GluCl) in complex with Fab, ivermectin and picrotoxin
Structural highlights
Publication Abstract from PubMedFast inhibitory neurotransmission is essential for nervous system function and is mediated by binding of inhibitory neurotransmitters to receptors of the Cys-loop family embedded in the membranes of neurons. Neurotransmitter binding triggers a conformational change in the receptor, opening an intrinsic chloride channel and thereby dampening neuronal excitability. Here we present the first three-dimensional structure, to our knowledge, of an inhibitory anion-selective Cys-loop receptor, the homopentameric Caenorhabditis elegans glutamate-gated chloride channel alpha (GluCl), at 3.3 A resolution. The X-ray structure of the GluCl-Fab complex was determined with the allosteric agonist ivermectin and in additional structures with the endogenous neurotransmitter l-glutamate and the open-channel blocker picrotoxin. Ivermectin, used to treat river blindness, binds in the transmembrane domain of the receptor and stabilizes an open-pore conformation. Glutamate binds in the classical agonist site at subunit interfaces, and picrotoxin directly occludes the pore near its cytosolic base. GluCl provides a framework for understanding mechanisms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors. Principles of activation and permeation in an anion-selective Cys-loop receptor.,Hibbs RE, Gouaux E Nature. 2011 May 15. PMID:21572436[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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