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The Journal of Neuroscience, August 1, 1998, 18(15):5555-5564

Formation of the Nicotinic Acetylcholine Receptor Binding Sites

William N. Green and Christian P. Wanamaker

Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637

Nicotinic acetylcholine receptors (AChRs) are activated by ACh binding to two sites located on different  subunits. The two  subunits, and , are distinguished by their interface with  and  subunits. We have characterized the formation of the ACh binding sites and found, contrary to the current model, that the sites form at different times and in a set order. The first site forms on subunits during the process of subunit assembly. Our data are consistent with the appearance of this site on subunit tetramers soon after the site for the competitive antagonist -bungarotoxin has formed and  subunits have assembled with trimers. The second site is located on subunits and forms after AChR subunits have assembled into ₂ pentamers. By determining the order in which the ACh binding sites form, we have also identified the sites in which the  and second subunits associate during subunit assembly.

Key words: protein folding and assembly; acetylcholine; -bungarotoxin; nicotinic receptors; pharmacology; ligand binding sites

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18155555-10$05.00/0

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