Identification of two critical residues within the Cys-loop sequence that determine fast-gating kinetics in a pentameric ligand-gated ion channel.
Pentameric ligand-gated ion channels (LGICs) are fast-gating receptors, represented by cationic nicotinic acetylcholine (nAChR) and serotonin (5HT3R) receptors, and by anionic GABA and glycine (GlyR) receptors. Because of a highly conserved sequence of 13 amino acids flanked by two canonical cysteine residues shared by all members of the family, these receptors are also known as the Cys-loop family. These receptors are allosteric transmembrane proteins made of five identical (or not) subunits arranged (pseudo) symmetrically around a central ion pore in the membrane. In nAChR, upon ACh binding, the receptor interconverts into discrete allosteric states, with each state corresponding to a different physiological state: resting (closed), active (open), and desensitized (closed).
Grutter
Thomas
T
Laboratoire Récepteurs et Cognition, Institut Pasteur, Paris, France. grutter@pasteur.fr
de Carvalho
Lia Prado
LP
Dufresne
Virginie
V
Taly
Antoine
A
Changeux
Jean-Pierre
JP
D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine; D015640:Ion Channel Gating / Q000502:physiology*; D008024:Ligands; D050506:Mutant Chimeric Proteins / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000502:physiology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*
D008024:Ligands; D050506:Mutant Chimeric Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D003545:Cysteine