This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4tnw

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab and POPC in a lipid-modulated conformation

Structural highlights

4tnw is a 30 chain structure with sequence from Caenorhabditis elegans and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4tnw"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4tnw]] 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=4TNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TNW FirstGlance]. <br>
-</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=4tnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tnw OCA], [https://pdbe.org/4tnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tnw RCSB], [https://www.ebi.ac.uk/pdbsum/4tnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tnw ProSAT]</span></td></tr>
 </table>

4tnw

From Proteopedia

Current revision

C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab and POPC in a lipid-modulated conformation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox