Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Complete list of metadatas

Cited literature [49 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01721946
Contributor : Ana Cova Rodrigues <>
Submitted on : Friday, March 2, 2018 - 5:36:06 PM
Last modification on : Wednesday, June 24, 2020 - 12:40:12 PM
Long-term archiving on: : Thursday, May 31, 2018 - 8:29:50 PM

File

E3028.full.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Collections

Citation

Radovan Spurny, Joachim Ramerstorfer, Kerry Price, Marijke Brams, Margot Ernst, et al.. Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2012, 109 (44), pp.E3028 - E3034. ⟨10.1073/pnas.1208208109⟩. ⟨pasteur-01721946⟩

Share

Metrics

Record views

499

Files downloads

300