3RIA: C. Elegans Glutamate-gated Chloride Channel (glucl) In Complex With Fab, Ivermectin And Iodide

Citation:
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 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.
PDB ID: 3RIADownload
MMDB ID: 90868
PDB Deposition Date: 2011/4/13
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 3.8  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3RIA: pentadecameric; determined by author and by software (PISA)
Molecular Components in 3RIA
Label Count Molecule
Proteins (15 molecules)
5
Avermectin-sensitive Glutamate-gated Chloride Channel Glucl Alpha
Molecule annotation
5
Mouse Monoclonal FAB Fragment, Heavy Chain
Molecule annotation
5
Mouse Monoclonal FAB Fragment, Light Chain
Molecule annotation
Chemicals (17 molecules)
1
5
2
3
3
4
4
3
5
1
6
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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