A single residue in the M2-M3 loop is a major determinant of coupling between binding and gating in neuronal nicotinic receptors.

• DOI: 10.1073/pnas.93.12.6118
• Publication Date: 2002-07-26T14:34:16Z
• Authors: A Campos-Caro; S Sala; J J Ballesta; F Vicente-Agulló; M Criado; F Sala
• Keywords: Cys-loop receptors; Nicotinic Antagonist

Binding of agonists to nicotinic acetylcholine receptors generates a sequence changes that activate cation-selective conductance. By measuring electrophysiological responses in chimeric alpha7/alpha3 expressed Xenopus oocytes, we have showed the involvement M2-M3 loop coupling agonist binding channel gate. An aspartate residue therein, Asp-266 alpha7 subunit, was identified by site-directed mutagenesis as crucial, since mutants at this position exhibited very poor functional three different agonists. We extended investigation another neuronal receptor (alpha3/beta4), and found homologous beta4 Asp-268, played similar role coupling. These findings are consistent with hypothesis loop, which is conserved all homomer-forming alpha-type subunits beta-type combine form receptors, major determinant information transmission from site gate receptors.