Pore Conformations and Gating Mechanism of a Cys-Loop Receptor

Neurons regulate the propagation of chemoelectric signals throughout the nervous system by opening and closing ion channels, a process known as gating. Here, histidine-based metal-binding sites were engineered along the intrinsic pore of a chimeric Cys-loop receptor to probe state-dependent$Zn^{2+}-...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-11, Vol.102 (44), p.15877-15882
Main Authors: Paas, Yoav, Gilad Gibor, Grailhe, Regis, Nathalie Savatier-Duclert, Dufresne, Virginie, Morten Sunesen, Lia Prado de Carvalho, Changeux, Jean-Pierre, Attali, Bernard
Format: Article
Language:English
Subjects:
Animals
Binding sites
Biological Sciences
Biophysics
Cell Line
Cell Membrane Permeability
Chimeras
Cholinergic receptors
Electric current
Electric potential
Electrophysiology
Girdles
Humans
Ion Channel Gating
Ion Channels
Ion Channels - chemistry
Ion Channels - physiology
Ions
Life Sciences
Membranes
Molecular structure
Neurobiology
Neurons
Neurons - chemistry
Neurons and Cognition
Oocytes
Porosity
Protein Conformation
Protein Engineering
Receptors
Receptors, Cholinergic
Receptors, Cholinergic - chemistry
Recombinant Fusion Proteins
Signal transduction
Steady state current
Xenopus
Zinc
Zinc - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neurons regulate the propagation of chemoelectric signals throughout the nervous system by opening and closing ion channels, a process known as gating. Here, histidine-based metal-binding sites were engineered along the intrinsic pore of a chimeric Cys-loop receptor to probe state-dependent$Zn^{2+}-channel$interactions. Patterns of Zn2+ion binding within the pore reveal that, in the closed state, the five pore-lining segments adopt an oblique orientation relative to the axis of ion conduction and constrict into a physical gate at their intracellular end. The interactions of Zn2+with the open state indicate that the five pore-lining segments should rigidly tilt to enable the movement of their intracellular ends away from the axis of ion conduction, so as to open the constriction (i.e., the gate). Alignment of the functional results with the 3D structure of an acetylcholine receptor allowed us to generate structural models accounting for the closed and open pore conformations and for a gating mechanism of a Cys-loop receptor.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507599102