4hfh: Difference between revisions
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==The GLIC pentameric Ligand-Gated Ion Channel (wild-type) complexed to bromoform== | |||
<StructureSection load='4hfh' size='340' side='right' caption='[[4hfh]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4hfh]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Gloeobacter_violaceus_pcc_7421 Gloeobacter violaceus pcc 7421]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HFH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HFH FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=MBR:TRIBROMOMETHANE'>MBR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PLC:DIUNDECYL+PHOSPHATIDYL+CHOLINE'>PLC</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hfb|4hfb]], [[4hfc|4hfc]], [[4hfd|4hfd]], [[4hfe|4hfe]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glvI, glr4197 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=251221 Gloeobacter violaceus PCC 7421])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hfh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hfh RCSB], [http://www.ebi.ac.uk/pdbsum/4hfh PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/GLIC_GLOVI 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.<ref>PMID:17167423</ref> | [[http://www.uniprot.org/uniprot/GLIC_GLOVI 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.<ref>PMID:17167423</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:23591864</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gloeobacter violaceus pcc 7421]] | [[Category: Gloeobacter violaceus pcc 7421]] | ||
[[Category: Corringer, P J | [[Category: Corringer, P J]] | ||
[[Category: Delarue, M | [[Category: Delarue, M]] | ||
[[Category: Harris, R A | [[Category: Harris, R A]] | ||
[[Category: Howard, R J | [[Category: Howard, R J]] | ||
[[Category: Lee, U S | [[Category: Lee, U S]] | ||
[[Category: Malherbe, L | [[Category: Malherbe, L]] | ||
[[Category: Sauguet, L | [[Category: Sauguet, L]] | ||
[[Category: Ion channel]] | [[Category: Ion channel]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
[[Category: Pentameric transmembrane channel]] | [[Category: Pentameric transmembrane channel]] | ||
[[Category: Transport protein]] | [[Category: Transport protein]] | ||
Revision as of 01:10, 25 December 2014
The GLIC pentameric Ligand-Gated Ion Channel (wild-type) complexed to bromoformThe GLIC pentameric Ligand-Gated Ion Channel (wild-type) complexed to bromoform
Structural highlights
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 PubMedEthanol 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
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