4HFE

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

Summary for 4HFE

• Entry DOI: 10.2210/pdb4hfe/pdb
• Related: 4HFB 4HFC 4HFD 4HFH
• Descriptor: Proton-gated ion channel, ACETATE ION, CHLORIDE ION, ... (9 entities in total)
• Functional Keywords: pentameric transmembrane channel, ion-channel, membrane protein, transport protein
• Biological source: Gloeobacter violaceus
• Cellular location: Cell inner membrane; Multi-pass membrane protein (Probable): Q7NDN8
• Total number of polymer chains: 5
• Total formula weight: 188463.01

Authors

Sauguet, L.,Howard, R.J.,Malherbe, L.,Lee, U.S.,Corringer, P.J.,Harris, R.A.,Delarue, M. (deposition date: 2012-10-05, release date: 2013-04-17, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)