Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2005 Nov 01;10244:15877-82. doi: 10.1073/pnas.0507599102.
Show Gene links
Show Anatomy links
Pore conformations and gating mechanism of a Cys-loop receptor.
Paas Y, Gibor G, Grailhe R, Savatier-Duclert N, Dufresne V, Sunesen M, de Carvalho LP, Changeux JP, Attali B.
???displayArticle.abstract???
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 Zn(2+) 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 Zn(2+) 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.
Betz,
Ligand-gated ion channels in the brain: the amino acid receptor superfamily.
1990, Pubmed
Betz,
Ligand-gated ion channels in the brain: the amino acid receptor superfamily.
1990,
Pubmed Bourne,
Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors.
2005,
Pubmed Bouzat,
Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel.
2004,
Pubmed Castaldo,
A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists.
2004,
Pubmed Celie,
Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures.
2004,
Pubmed Chakrapani,
Gating dynamics of the acetylcholine receptor extracellular domain.
2004,
Pubmed Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed Eiselé,
Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities.
1993,
Pubmed
,
Xenbase Gibor,
External barium affects the gating of KCNQ1 potassium channels and produces a pore block via two discrete sites.
2004,
Pubmed
,
Xenbase Horenstein,
Protein mobility and GABA-induced conformational changes in GABA(A) receptor pore-lining M2 segment.
2001,
Pubmed
,
Xenbase Hu,
Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating.
2003,
Pubmed Karlin,
Emerging structure of the nicotinic acetylcholine receptors.
2002,
Pubmed Kash,
Coupling of agonist binding to channel gating in the GABA(A) receptor.
2003,
Pubmed Kearney,
Determinants of nicotinic receptor gating in natural and unnatural side chain structures at the M2 9' position.
1996,
Pubmed
,
Xenbase Langosch,
Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia.
1994,
Pubmed
,
Xenbase Laube,
Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses?
2002,
Pubmed Leonard,
Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor.
1988,
Pubmed
,
Xenbase Lester,
Cys-loop receptors: new twists and turns.
2004,
Pubmed Lynch,
The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.
2001,
Pubmed Miyazawa,
Structure and gating mechanism of the acetylcholine receptor pore.
2003,
Pubmed Neher,
Local anaesthetics transiently block currents through single acetylcholine-receptor channels.
1978,
Pubmed Panicker,
Minimal structural rearrangement of the cytoplasmic pore during activation of the 5-HT3A receptor.
2004,
Pubmed
,
Xenbase Pascual,
Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel.
1998,
Pubmed
,
Xenbase Taly,
Normal mode analysis suggests a quaternary twist model for the nicotinic receptor gating mechanism.
2005,
Pubmed Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed Wilson,
Acetylcholine receptor channel structure in the resting, open, and desensitized states probed with the substituted-cysteine-accessibility method.
2001,
Pubmed
,
Xenbase Wilson,
The location of the gate in the acetylcholine receptor channel.
1998,
Pubmed
