Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor

BAIER, C.J.; FANTINI, J.; BARRANTES, F.J.

Scientific Reports

Nature Publishing Group

Año: 2011 vol. 1 p. 1 - 7

2045-2322

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.mol21, adding up to a total of about 200 kJ.mol21 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 itcould be responsible for some of the above structural/functional properties of the AChR.