title: Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor.
abstract: Cholesterol influences ion-channel function, distribution and clustering in the membrane, endocytosis, and exocytic sorting of the nicotinic acetylcholine receptor (AChR). We report the occurrence of a cholesterol recognition motif, here coined "CARC", in the transmembrane regions of AChR subunits that bear extensive contact with the surrounding lipid, and are thus optimally suited to convey cholesterol-mediated signaling from the latter. Three cholesterol molecules could be docked on the transmembrane segments of each AChR subunit, rendering a total of 15 cholesterol molecules per AChR molecule. The CARC motifs contribute each with an energy of interaction between 35 and 52 kJ.mol(-1), adding up to a total of about 200 kJ.mol(-1) per receptor molecule, i.e. ∼40% of the lipid solvation free energy/ AChR molecule. The CARC motif is remarkably conserved along the phylogenetic scale, from prokaryotes to human, suggesting that it could be responsible for some of the above structural/functional properties of the AChR.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Baier
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Barrantes
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011978:Receptors, Nicotinic; D002784:Cholesterol