ABSTRACT
High-resolution X-ray diffraction structures of integral membrane proteins have revealed various binding modes of lipids, but current spectroscopic studies still use uniform macroscopic binding constants to describe lipid binding. The Adair approach employing microscopic lipid-binding constants has previously been taken to explain the enhancement of agonist binding to the nicotinic acetylcholine receptor by general anaesthetics in terms of the competitive displacement of essential lipid activator molecules [Walcher S, Altschuh J & Sandermann H (2001) J. Biol. Chem.276, 42191-42195]. This approach was extended to tadpole narcosis induced by alcohols. A single class, or two different classes of lipid activator binding sites, are considered. Microscopic lipid and inhibitor binding constants are derived and allow a close fit to dose-response curves of tadpole narcosis on the basis of a preferential displacement of more loosely bound essential lipid activator molecules. This study illustrates the potential of the Adair approach to resolve protein-bound lipid populations.
