WATER-SOLUBLE NICOTINIC ACETYLCHOLINE-RECEPTOR FORMED BY ALPHA-7 SUBUNIT EXTRACELLULAR DOMAINS

Water-soluble models of ligand gated ion channels would be advantageou s for structural studies. We investigated the suitability of three ver sions of the N-terminal extracellular domain (ECD) of the alpha 7 subu nit of the nicotinic acetylcholine receptor (AChR) family for this pur pose by examining their ligand-binding and assembly properties. Two ve rsions included the first transmembrane domain and were solubilized wi th detergent after expression in Xenopus oocytes. The third was trunca ted before the first transmembrane domain and was soluble without dete rgent. For all three, their equilibrium binding affinities for alpha-b ungarotoxin, nicotine, and acetylcholine, combined with their velocity sedimentation profiles, were consistent with the formation of native- like AChRs. These characteristics imply that the alpha 7 ECD can form a water-soluble AChR that is a model of the ECD of the full-length alp ha 7 AChR.