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Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels mediating fast cholinergic synaptic transmission in the brain and at neuromuscular junctions. We used the structure of the acetylcholine binding protein from Lymnaea stagnalis to model the chicken alpha7 agonist-binding domain. The initial models and a preliminary docking study suggested that position Leu118 may play an important role in determining agonist actions on alpha7. A prediction from these in silico studies, that L118E and L118D would retain binding to acetylcholine but L118K and L118R would not, was confirmed in electrophysiological studies on functional recombinant mutant receptors expressed in Xenopus laevis oocytes. The functional studies also demonstrated that residues at position 118 have a dramatic effect on the actions of imidacloprid (a partial agonist of wild-type alpha7 receptors) and its des-nitro derivative. Molecular dynamics simulations confirmed that Leu118 can strongly influence agonist binding and that the model was robust in terms of its prediction for acetylcholine binding. Together, the results indicate a role for Leu118 in influencing agonist actions on alpha7 nAChRs.

Original publication




Journal article


Mol Pharmacol

Publication Date





1659 - 1667


Amino Acid Sequence, Animals, Chickens, Dose-Response Relationship, Drug, Female, Leucine, Molecular Sequence Data, Nicotinic Agonists, Protein Binding, Protein Structure, Tertiary, Receptors, Nicotinic, Xenopus laevis, alpha7 Nicotinic Acetylcholine Receptor