title: Thinking in cycles: MWC is a good model for acetylcholine receptor-channels.
abstract: Neuromuscular acetylcholine receptors have long been a model system for understanding the mechanisms of operation of ligand-gated ion channels and fast chemical synapses. These five subunit membrane proteins have two allosteric (transmitter) binding sites and a distant ion channel domain. Occupation of the binding sites by agonist molecules transiently increases the probability that the channel is ion-permeable. Recent experiments show that the Monod, Wyman and Changeux formalism for allosteric proteins, originally developed for haemoglobin, is an excellent model for acetylcholine receptors. By using mutations and single-channel electrophysiology, the gating equilibrium constants for receptors with zero, one or two bound agonist molecules, and the agonist association and dissociation rate constants from both the closed- and open-channel conformations, have been estimated experimentally. The change in affinity for each transmitter molecule between closed and open conformations provides ~-5.1 kcal mol(-1) towards the global gating isomerization of the protein.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA. auerbach@buffalo.edu
authors.forename: Anthony
authors.initials: A
authors.lastname: Auerbach
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D058446:Ligand-Gated Ion Channels / Q000378:metabolism*; D008954:Models, Biological; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D058446:Ligand-Gated Ion Channels; D011950:Receptors, Cholinergic