3RIF

C. elegans glutamate-gated chloride channel (GluCl) in complex with Fab, ivermectin and glutamate.

Summary for 3RIF

• Entry DOI: 10.2210/pdb3rif/pdb
• Related: 3RHW 3RI5 3RIA
• Descriptor: Avermectin-sensitive glutamate-gated chloride channel GluCl alpha, UNDECANE, Mouse monoclonal Fab fragment, heavy chain, ... (10 entities in total)
• Functional Keywords: membrane protein, transport protein, cys-loop receptor, ligand-gated ion channel, neurotransmitter receptor, ivermectin, picrotoxin, glycosylation, transport protein-immune system complex, transport protein/immune system
• Biological source: Caenorhabditis elegans (nematode); More
• Total number of polymer chains: 15
• Total formula weight: 438723.67

Authors

Hibbs, R.E.,Gouaux, E. (deposition date: 2011-04-13, release date: 2011-05-25, Last modification date: 2024-11-20)

Primary citation

Hibbs, R.E.,Gouaux, E.
Principles of activation and permeation in an anion-selective Cys-loop receptor.
Nature, 474:54-60, 2011

PubMed 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.

PubMed: 21572436
DOI: 10.1038/nature10139

Experimental method

X-RAY DIFFRACTION (3.345 Å)