Epitopes described in "Principles of activation and permeation in an anion-selective Cys-loop receptor."

Article Authors:Ryan E Hibbs; Eric Gouaux
Article Title:Principles of activation and permeation in an anion-selective Cys-loop receptor.
Reference Detail
Reference ID:1022182
Abstract:Fast 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 (GluCl), at 3.3 Å 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.
Affiliations:Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Reference Type:Literature
PubMed ID:21572436
Journal Volume:474
Article Pages:54-60
Journal ISSN:1476-4687
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@618e3c73;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4122d40e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5590048a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@621a2be8;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2438bea9;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@96d5bd3
Article MeSH List:Animals; Anions; Binding Sites; Caenorhabditis elegans(metabolism); Chloride Channels(chemistry; metabolism); Cysteine Loop Ligand-Gated Ion Channel Receptors(metabolism); Ions(metabolism); Models, Molecular; Neurotransmitter Agents(metabolism); Protein Structure, Tertiary
Curation Last Updated:2015-01-18 20:04:49