4hfe | pdb_00004hfe

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

spinqualitylabelsall models 4hfe, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hfe is a 5 chain structure with sequence from Gloeobacter violaceus PCC 7421. The November 2015 RCSB PDB Molecule of the Month feature on Glutamate-gated Chloride Receptors by David Goodsell is 10.2210/rcsb_pdb/mom_2015_11. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, EOH, LMT, NA, PLC, UNL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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