Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.
Introduction by site-directed mutagenesis of three amino acids from the MII segment of glycine or gamma-aminobutyric acid (GABAA) receptors into the MII segment of alpha 7 nicotinic receptor was sufficient to convert a cation-selective channel into an anion-selective channel gated by acetylcholine. A critical mutation was the insertion of an uncharged residue at the amino-terminal end of MII, stressing the importance of protein geometrical constraints on ion selectivity.
Galzi
J L
JL
Unité de Recherche Associée au Centre National de la Recherche Scientifique D1284, Institut Pasteur, Paris, France.
Devillers-Thiéry
A
A
Hussy
N
N
Bertrand
S
S
Changeux
J P
JP
Bertrand
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions; D002118:Calcium; D002412:Cations; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000737:chemistry*; D009865:Oocytes / Q000378:metabolism; D010539:Permeability; D011963:Receptors, GABA-A / Q000737:chemistry; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014981:Xenopus
D000838:Anions; D002412:Cations; D002614:Chelating Agents; D007473:Ion Channels; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D011978:Receptors, Nicotinic; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D002118:Calcium