4HFC

The GLIC pentameric Ligand-Gated Ion Channel F14'A ethanol-sensitive mutant complexed to 2-bromo-ethanol

4HFC の概要

• エントリーDOI: 10.2210/pdb4hfc/pdb
• 関連するPDBエントリー: 4HFB
• 分子名称: Proton-gated ion channel, DODECYL-BETA-D-MALTOSIDE, 2-BROMOETHANOL, ... (8 entities in total)
• 機能のキーワード: pentameric transmembrane channel, ion-channel, membrane protein, transport protein
• 由来する生物種: Gloeobacter violaceus
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein (Probable): Q7NDN8
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 188562.28

構造登録者

Sauguet, L.,Howard, R.J.,Malherbe, L.,Lee, U.S.,Corringer, P.J.,Harris, R.A.,Delarue, M. (登録日: 2012-10-05, 公開日: 2013-04-17, 最終更新日: 2024-02-28)

主引用文献

Sauguet, L.,Howard, R.J.,Malherbe, L.,Lee, U.S.,Corringer, P.J.,Harris, R.A.,Delarue, M.
Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel.
Nat Commun, 4:1697-1697, 2013

PubMed Abstract: Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol.

PubMed: 23591864
DOI: 10.1038/ncomms2682

実験手法

X-RAY DIFFRACTION (3.05 Å)