title: Anionic lipids allosterically modulate multiple nicotinic acetylcholine receptor conformational equilibria.
abstract: Anionic lipids influence the ability of the nicotinic acetylcholine receptor to gate open in response to neurotransmitter binding, but the underlying mechanisms are poorly understood. We show here that anionic lipids with relatively small headgroups, and thus the greatest ability to influence lipid packing/bilayer physical properties, are the most effective at stabilizing an agonist-activatable receptor. The differing abilities of anionic lipids to stabilize an activatable receptor stem from differing abilities to preferentially favor resting over both uncoupled and desensitized conformations. Anionic lipids thus modulate multiple acetylcholine receptor conformational equilibria. Our data suggest that both lipids and membrane physical properties act as classic allosteric modulators influencing function by interacting with and thus preferentially stabilizing different native acetylcholine receptor conformational states.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Corrie J B
authors.initials: CJ
authors.lastname: daCosta
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Medaglia
authors.forename: Nadine
authors.initials: N
authors.lastname: Lavigne
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Wang
authors.forename: Casey L
authors.initials: CL
authors.lastname: Carswell
authors.forename: John E
authors.initials: JE
authors.lastname: Baenziger
mesh_terms: D000495:Allosteric Site; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001703:Biophysics / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism; D002855:Chromatography, Thin Layer / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008954:Models, Biological; D008968:Molecular Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry*; D013055:Spectrophotometry, Infrared / Q000379:methods; D014101:Torpedo
chemical_list: D000838:Anions; D008051:Lipid Bilayers; D008055:Lipids; D011978:Receptors, Nicotinic