TY - JOUR
T1 - Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor
AU - Blount, Paul
AU - Merlie, John Paul
N1 - Funding Information:
P B. was supported by National Research Service Award 2 T32 GM 07805. This work was also supported by funds from the Senator Jacob Javits Center of Excellence in Neurosciences and grants from the National Institutes of Health and the Muscular Dystrophy Association of America.
PY - 1989/9
Y1 - 1989/9
N2 - We have stably expressed in fibroblasts different pairs of α and non-α subunits of the mouse muscle nicotinic acetylcholine receptor (AChR). The γ and δ, but not the β, subunits associated efficiently with the α subunit, and they extensively modified its binding characteristics. The αγ and αδ complexes formed distinctly different high affinity binding sites for the competitive antagonist d-tubocurarine that, together, completely accounted for the two nonequivalent antagonist binding sites in native AChR. The αδ complex and native AChR had similar affinities for the agonist carbamylcholine. In contrast, although the ay complex contains the higher affinity competitive antagonist binding site, it had an affinity for carbamylcholine that was an order of magnitude less than that of the αδ complex or the AChR. The comparatively low agonist affinity of the αγ complex may represent an allosterically regulated binding site in the native AChR. These data support a model of two nonequivalent binding sites within the AChR and imply that the basis for this nonequivalence is the association of the a subunit with the γ or δ subunit.
AB - We have stably expressed in fibroblasts different pairs of α and non-α subunits of the mouse muscle nicotinic acetylcholine receptor (AChR). The γ and δ, but not the β, subunits associated efficiently with the α subunit, and they extensively modified its binding characteristics. The αγ and αδ complexes formed distinctly different high affinity binding sites for the competitive antagonist d-tubocurarine that, together, completely accounted for the two nonequivalent antagonist binding sites in native AChR. The αδ complex and native AChR had similar affinities for the agonist carbamylcholine. In contrast, although the ay complex contains the higher affinity competitive antagonist binding site, it had an affinity for carbamylcholine that was an order of magnitude less than that of the αδ complex or the AChR. The comparatively low agonist affinity of the αγ complex may represent an allosterically regulated binding site in the native AChR. These data support a model of two nonequivalent binding sites within the AChR and imply that the basis for this nonequivalence is the association of the a subunit with the γ or δ subunit.
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U2 - 10.1016/0896-6273(89)90259-6
DO - 10.1016/0896-6273(89)90259-6
M3 - Article
C2 - 2642001
AN - SCOPUS:0024725677
SN - 0896-6273
VL - 3
SP - 349
EP - 357
JO - Neuron
JF - Neuron
IS - 3
ER -