Publication Date:
2008-11-07
Description:
Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 A constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation, shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular beta-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 alpha-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bocquet, Nicolas -- Nury, Hugues -- Baaden, Marc -- Le Poupon, Chantal -- Changeux, Jean-Pierre -- Delarue, Marc -- Corringer, Pierre-Jean -- England -- Nature. 2009 Jan 1;457(7225):111-4. doi: 10.1038/nature07462. Epub 2008 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pasteur Institute, G5 Group of Channel-Receptor, CNRS URA 2182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987633" target="_blank"〉PubMed〈/a〉
Keywords:
Crystallography, X-Ray
;
Cyanobacteria/*chemistry
;
Hydrophobic and Hydrophilic Interactions
;
*Ion Channel Gating
;
Ion Channels/*chemistry/*metabolism
;
Ligands
;
Models, Molecular
;
Pectobacterium chrysanthemi/chemistry
;
Protein Structure, Quaternary
;
Protein Subunits/chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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