Gamma- and delta-subunits regulate the affinity and the cooperativity of ligand binding to the acetylcholine receptor.
The acetylcholine receptor (AChR) from vertebrate skeletal muscle is a pentamer composed of two ligand-binding alpha-subunits and one beta-, gamma-, and delta-subunit. To examine the functional roles of the non-alpha-subunits, we have expressed, in stable cell lines, AChRs lacking either a gamma- or a delta-subunit. Most previous work has examined how these changes in subunit composition affect single channel properties. Here, we take advantage of the stable expression system to produce large amounts of AChR and, for the first time, examine ligand binding to altered AChRs on intact cells. The changes in subunit composition affect both ligand affinity and cooperativity of the receptor, suggesting important roles for the gamma- and delta-subunits, both in shaping the ligand binding site and maintaining cooperative interactions between alpha-subunits.
Sine
S M
SM
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Claudio
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D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002217:Carbachol / Q000378:metabolism; D002460:Cell Line; D003064:Cnidarian Venoms / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D008024:Ligands; D051379:Mice; D003473:Neuromuscular Nondepolarizing Agents / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013729:Terpenes; D014403:Tubocurarine / Q000031:analogs & derivatives / Q000378:metabolism
D003064:Cnidarian Venoms; D008024:Ligands; D003473:Neuromuscular Nondepolarizing Agents; D011950:Receptors, Cholinergic; D013729:Terpenes; C030303:lophotoxin; D002217:Carbachol; C015836:dimethyltubocurarine; D014403:Tubocurarine