Document Detail

Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.
MedLine Citation:
PMID:  23035248     Owner:  NLM     Status:  MEDLINE    
GABA(A) receptors are pentameric ligand-gated ion channels involved in fast inhibitory neurotransmission and are allosterically modulated by the anxiolytic, anticonvulsant, and sedative-hypnotic benzodiazepines. Here we show that the prokaryotic homolog ELIC also is activated by GABA and is modulated by benzodiazepines with effects comparable to those at GABA(A) receptors. Crystal structures reveal important features of GABA recognition and indicate that benzodiazepines, depending on their concentration, occupy two possible sites in ELIC. An intrasubunit site is adjacent to the GABA-recognition site but faces the channel vestibule. A second intersubunit site partially overlaps with the GABA site and likely corresponds to a low-affinity benzodiazepine-binding site in GABA(A) receptors that mediates inhibitory effects of the benzodiazepine flurazepam. Our study offers a structural view how GABA and benzodiazepines are recognized at a GABA-activated ion channel.
Radovan Spurny; Joachim Ramerstorfer; Kerry Price; Marijke Brams; Margot Ernst; Hugues Nury; Mark Verheij; Pierre Legrand; Daniel Bertrand; Sonia Bertrand; Dennis A Dougherty; Iwan J P de Esch; Pierre-Jean Corringer; Werner Sieghart; Sarah C R Lummis; Chris Ulens
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-01     Completed Date:  2013-01-08     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E3028-34     Citation Subset:  IM    
Department of Cellular and Molecular Medicine, Laboratory of Structural Neurobiology, Catholic University of Leuven, 3000 Leuven, Belgium.
Data Bank Information
Bank Name/Acc. No.:
PDB/4A96;  4A97;  4A98
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MeSH Terms
Benzodiazepines / metabolism,  pharmacology*
Binding Sites
Crystallography, X-Ray
Ion Channel Gating / drug effects*
Ion Channels / chemistry,  metabolism*
Models, Molecular
Receptors, GABA-A / metabolism
gamma-Aminobutyric Acid / metabolism*
Grant Support
NS 34407/NS/NINDS NIH HHS; //Wellcome Trust
Reg. No./Substance:
0/Biopolymers; 0/Ion Channels; 0/Ligands; 0/Receptors, GABA-A; 12794-10-4/Benzodiazepines; 56-12-2/gamma-Aminobutyric Acid

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