Structural highlights
4hfe is a 5 chain structure with sequence from Gloeobacter violaceus pcc 7421. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , |
| Related: | 4hfb, 4hfc, 4hfd, 4hfh |
| Gene: | glvI, glr4197 (Gloeobacter violaceus PCC 7421) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[GLIC_GLOVI] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.[1]
Publication Abstract from PubMed
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.
Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel.,Sauguet L, Howard RJ, Malherbe L, Lee US, Corringer PJ, Harris RA, Delarue M Nat Commun. 2013;4:1697. doi: 10.1038/ncomms2682. PMID:23591864[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, Taly A, Grutter T, Changeux JP, Corringer PJ. A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature. 2007 Jan 4;445(7123):116-9. Epub 2006 Dec 10. PMID:17167423 doi:10.1038/nature05371
- ↑ Sauguet L, Howard RJ, Malherbe L, Lee US, Corringer PJ, Harris RA, Delarue M. Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nat Commun. 2013;4:1697. doi: 10.1038/ncomms2682. PMID:23591864 doi:10.1038/ncomms2682
