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| | <StructureSection load='4tnv' size='340' side='right'caption='[[4tnv]], [[Resolution|resolution]] 3.60Å' scene=''> | | <StructureSection load='4tnv' size='340' side='right'caption='[[4tnv]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tnv]] is a 30 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TNV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tnv]] is a 30 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TNV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tnw|4tnw]], [[3rhw|3rhw]], [[3ri5|3ri5]], [[3ria|3ria]], [[3rif|3rif]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tnv OCA], [https://pdbe.org/4tnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tnv RCSB], [https://www.ebi.ac.uk/pdbsum/4tnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tnv ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glc-1, CELE_F11A5.10, F11A5.10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tnv OCA], [http://pdbe.org/4tnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tnv RCSB], [http://www.ebi.ac.uk/pdbsum/4tnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tnv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GLUCL_CAEEL GLUCL_CAEEL] Glutamate-gated chloride channel subunit; channel properties depend on the subunit composition. Glutamate binding triggers a rapidly reversible current in heteromeric channels formed by glc-1 and glc-2, while the anti-helmintic drug ivermectin and other avermectins trigger a permanently open channel configuration. Channels containing only glc-1 are activated by ivermectin, but not by glutamate alone (in vitro). The heteromeric channel formed by glc-1 and glc-2 is also activated by ibotenate, and it is blocked by picrotoxin and flufenamic acid (PubMed:7935817). Plays a role in the regulation of locomotor behavior (PubMed:16527366).<ref>PMID:16527366</ref> <ref>PMID:21572436</ref> <ref>PMID:7935817</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Althoff, T]] | + | [[Category: Althoff T]] |
| - | [[Category: Banerjee, S]] | + | [[Category: Banerjee S]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Gouaux E]] |
| - | [[Category: Hibbs, R E]] | + | [[Category: Hibbs RE]] |
| - | [[Category: Cys-loop receptor]]
| + | |
| - | [[Category: Ligand-gated ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Neurotransmitter receptor]]
| + | |
| - | [[Category: Transport protein-immune system complex]]
| + | |
| Structural highlights
Function
GLUCL_CAEEL Glutamate-gated chloride channel subunit; channel properties depend on the subunit composition. Glutamate binding triggers a rapidly reversible current in heteromeric channels formed by glc-1 and glc-2, while the anti-helmintic drug ivermectin and other avermectins trigger a permanently open channel configuration. Channels containing only glc-1 are activated by ivermectin, but not by glutamate alone (in vitro). The heteromeric channel formed by glc-1 and glc-2 is also activated by ibotenate, and it is blocked by picrotoxin and flufenamic acid (PubMed:7935817). Plays a role in the regulation of locomotor behavior (PubMed:16527366).[1] [2] [3]
Publication Abstract from PubMed
Cys-loop receptors are neurotransmitter-gated ion channels that are essential mediators of fast chemical neurotransmission and are associated with a large number of neurological diseases and disorders, as well as parasitic infections. Members of this ion channel superfamily mediate excitatory or inhibitory neurotransmission depending on their ligand and ion selectivity. Structural information for Cys-loop receptors comes from several sources including electron microscopic studies of the nicotinic acetylcholine receptor, high-resolution X-ray structures of extracellular domains and X-ray structures of bacterial orthologues. In 2011 our group published structures of the Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in complex with the allosteric partial agonist ivermectin, which provided insights into the structure of a possibly open state of a eukaryotic Cys-loop receptor, the basis for anion selectivity and channel block, and the mechanism by which ivermectin and related molecules stabilize the open state and potentiate neurotransmitter binding. However, there remain unanswered questions about the mechanism of channel opening and closing, the location and nature of the shut ion channel gate, the transitions between the closed/resting, open/activated and closed/desensitized states, and the mechanism by which conformational changes are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane, ion channel domain. Here we present two conformationally distinct structures of C. elegans GluCl in the absence of ivermectin. Structural comparisons reveal a quaternary activation mechanism arising from rigid-body movements between the extracellular and transmembrane domains and a mechanism for modulation of the receptor by phospholipids.
X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors.,Althoff T, Hibbs RE, Banerjee S, Gouaux E Nature. 2014 Aug 21;512(7514):333-7. doi: 10.1038/nature13669. PMID:25143115[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cook A, Aptel N, Portillo V, Siney E, Sihota R, Holden-Dye L, Wolstenholme A. Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors. Mol Biochem Parasitol. 2006 May;147(1):118-25. PMID:16527366 doi:10.1016/j.molbiopara.2006.02.003
- ↑ Hibbs RE, Gouaux E. Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature. 2011 May 15. PMID:21572436 doi:10.1038/nature10139
- ↑ Cully DF, Vassilatis DK, Liu KK, Paress PS, Van der Ploeg LH, Schaeffer JM, Arena JP. Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature. 1994 Oct 20;371(6499):707-11. PMID:7935817 doi:10.1038/371707a0
- ↑ Althoff T, Hibbs RE, Banerjee S, Gouaux E. X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature. 2014 Aug 21;512(7514):333-7. doi: 10.1038/nature13669. PMID:25143115 doi:http://dx.doi.org/10.1038/nature13669
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