Formation of the Nicotinic Acetylcholine Receptor Binding Sites

W. N. Green,C. Wanamaker

Published 1998 in Journal of Neuroscience

ABSTRACT

Nicotinic acetylcholine receptors (AChRs) are activated by ACh binding to two sites located on different α subunits. The two α subunits, αγ and αδ, are distinguished by their interface with γ and δ 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 αγ subunits during the process of subunit assembly. Our data are consistent with the appearance of this site on αβγδ subunit tetramers soon after the site for the competitive antagonist α-bungarotoxin has formed and δ subunits have assembled with αβγ trimers. The second site is located on αδ subunits and forms after AChR subunits have assembled into α2βγδ pentamers. By determining the order in which the ACh binding sites form, we have also identified the sites in which the δ and second α subunits associate during subunit assembly.

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