期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1993
卷号：90
期号：13
页码：6285-6289
DOI：10.1073/pnas.90.13.6285
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In nicotinic receptors, the binding sites for acetylcholine are likely to contain negatively charged amino acid side chains that interact with the positively charged quaternary ammonium group of acetylcholine and of other potent agonists. We previously found that a 61-residue segment of the delta subunit contains aspartate or glutamate residues within 1 nm of cysteines in the acetylcholine binding site on the alpha subunit. We have now mutated, one at a time, the 12 aspartates and glutamates in this segment of the mouse muscle delta subunit and have expressed the mutant receptors in Xenopus oocytes. Both the concentration of acetylcholine eliciting half-maximal current (Kapp) and the Ki for the inhibition by acetylcholine of alpha-bungarotoxin binding were increased 100-fold by the mutation of delta Asp180 to Asn and 10-fold by the mutation of delta Glu189 to Gln. These two residues, and their homologs in the gamma and epsilon subunits, are likely to contribute to the acetylcholine binding sites.
