X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.
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.
Bocquet
Nicolas
N
Pasteur Institute, G5 Group of Channel-Receptor, CNRS URA 2182.
Nury
Hugues
H
Baaden
Marc
M
Le Poupon
Chantal
C
Changeux
Jean-Pierre
JP
Delarue
Marc
M
Corringer
Pierre-Jean
PJ
D018360:Crystallography, X-Ray; D000458:Cyanobacteria / Q000737:chemistry*; D016974:Dickeya chrysanthemi / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
D007473:Ion Channels; D008024:Ligands; D021122:Protein Subunits