title: Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor.
abstract: In the alpha7 nicotinic acetylcholine receptors, we analyze the contribution of mutations E237A and V251T, together with the proline insertion P236', in the conversion of the charge selectivity from cationic to anionic. We show that the triple mutant exhibits spontaneous openings displaying anionic selectivity. Furthermore, at position 251, hydrophilic or even negatively charged residues are compatible with an anionic channel. In contrast, the additional proline yields an anionic channel only when inserted between positions 234 and 237; insertion before 234 yields a cationic channel and after 238 alters the receptor surface expression. The coiled 234-238 loop thus directly contributes to the charge selectivity filter of the alpha7 channel.
authors.affiliation: Neurobiologie Moléculaire, Unité de Recherche Associée au Centre National de la Recherche Scientifique D1284, Institut Pasteur, Paris, France.
authors.forename: P J
authors.initials: PJ
authors.lastname: Corringer
authors.forename: S
authors.initials: S
authors.lastname: Bertrand
authors.forename: J L
authors.initials: JL
authors.lastname: Galzi
authors.forename: A
authors.initials: A
authors.lastname: Devillers-Thiéry
authors.forename: J P
authors.initials: JP
authors.lastname: Changeux
authors.forename: D
authors.initials: D
authors.lastname: Bertrand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions; D002412:Cations; D005374:Filtration; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011392:Proline / Q000032:analysis; D011978:Receptors, Nicotinic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D000838:Anions; D002412:Cations; D011978:Receptors, Nicotinic; D011392:Proline