3ri5: Difference between revisions
New page: '''Unreleased structure''' The entry 3ri5 is ON HOLD Authors: Hibbs, R.E., Gouaux, E. Description: C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab, ivermectin a... |
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==C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab, ivermectin and picrotoxin== | |||
<StructureSection load='3ri5' size='340' side='right'caption='[[3ri5]], [[Resolution|resolution]] 3.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ri5]] is a 15 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=3RI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RI5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</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=IVM:(2AE,4E,5S,6S,6R,7S,8E,11R,13R,15S,17AR,20R,20AR,20BS)-6-[(2S)-BUTAN-2-YL]-20,20B-DIHYDROXY-5,6,8,19-TETRAMETHYL-17-OXO-3,4,5,6,6,10,11,14,15,17,17A,20,20A,20B-TETRADECAHYDRO-2H,7H-SPIRO[11,15-METHANOFURO[4,3,2-PQ][2,6]BENZODIOXACYCLOOCTADECINE-13,2-PYRAN]-7-YL+2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>IVM</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>, <scene name='pdbligand=RI5:(1AR,2AR,3S,6R,6AS,8AS,8BR,9R)-2A-HYDROXY-8B-METHYL-9-(PROP-1-EN-2-YL)HEXAHYDRO-3,6-METHANO-1,5,7-TRIOXACYCLOPENTA[IJ]CYCLOPROPA[A]AZULENE-4,8(3H)-DIONE'>RI5</scene>, <scene name='pdbligand=UND:UNDECANE'>UND</scene></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=3ri5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ri5 OCA], [https://pdbe.org/3ri5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ri5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ri5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ri5 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 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<ref>PMID:21572436</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ri5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Art:Opening a Gate to Human Health|Art:Opening a Gate to Human Health]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Caenorhabditis elegans]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Gouaux E]] | |||
[[Category: Hibbs RE]] | |||
Latest revision as of 12:38, 30 October 2024
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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