Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Principles of activation and permeation in an anion-selective Cys-loop receptor.

Nature | Jun 2, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21572436

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 ID: 21572436 RIS Download

Mesh terms: Animals | Anions | Binding Sites | Caenorhabditis elegans | Chloride Channels | Cysteine Loop Ligand-Gated Ion Channel Receptors | Ions | Models, Molecular | Neurotransmitter Agents | Protein Structure, Tertiary

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: F32 NS061404
  • Agency: NINDS NIH HHS, Id: F32 NS061404-01
  • Agency: NINDS NIH HHS, Id: F32 NS061404-02
  • Agency: NINDS NIH HHS, Id: F32 NS061404-03
  • Agency: NINDS NIH HHS, Id: F32NS061404
  • Agency: NINDS NIH HHS, Id: P30 NS061800
  • Agency: Howard Hughes Medical Institute, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.