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© Marie Prévost, Institut Pasteur
Image of a portion of a Xenopus oocyte expressing a channel receptor.
Publication : Proceedings of the National Academy of Sciences of the United States of America

Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 03 Oct 2012

Spurny R, Ramerstorfer J, Price K, Brams M, Ernst M, Nury H, Verheij M, Legrand P, Bertrand D, Bertrand S, Dougherty DA, de Esch IJ, Corringer PJ, Sieghart W, Lummis SC, Ulens C

Link to Pubmed [PMID] – 23035248

Proc. Natl. Acad. Sci. U.S.A. 2012 Oct;109(44):E3028-34

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.

http://www.ncbi.nlm.nih.gov/pubmed/23035248