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| Article Authors: | Ryan E Hibbs; Eric Gouaux |
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| Article Title: | Principles of activation and permeation in an anion-selective Cys-loop receptor. |
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| Reference ID: | 1022182 |
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| 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 α (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. |
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| Affiliations: | Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. |
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| Date: | 2011 |
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| Reference Type: | Literature |
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| PubMed ID: | 21572436 |
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| Journal: | Nature |
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| Journal Volume: | 474 |
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| Article Pages: | 54-60 |
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| Journal ISSN: | 1476-4687 |
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| Article Chemical List: | Anions;Chloride Channels;Cysteine Loop Ligand-Gated Ion Channel Receptors;Ions;Neurotransmitter Agents;glutamate-gated chloride channels |
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| 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 |
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| Curation Last Updated: | 2012-05-31 20:50:34 |
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