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Ligand binding to the β-adrenergic receptor involves its rhodopsin-like core

Abstract

Recently the genes for several hormone receptors that interact with guanine nucleotide binding proteins (G proteins) have been cloned, including the hamster β2-adrenergic receptor (β2AR)1, a human β2AR2, the turkey erythrocyte β2AR3 and the porcine mus-carinic acetylcholine receptor (MAR)4. All these receptors share some amino-acid homology with rhodopsin, particularly in 7 hydro-phobic stretches of residues that are believed to represent trans-membrane helices5. To determine whether differences in ligand specificity result from the divergence in the sequences of the hydrophilic regions of these receptors, we have expressed in mammalian cells genes for the wild-type hamster and human βAR proteins, and a series of deletion mutant genes of the hamster β2AR. The pharmacology of the expressed receptors indicates that most of the hydrophilic residues are not directly involved in the binding of agonists or antagonists to the receptor. In addition, we have identified a mutant receptor that has high agonist affinity but does not couple to adenylate cyclase.

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Dixon, R., Sigal, I., Rands, E. et al. Ligand binding to the β-adrenergic receptor involves its rhodopsin-like core. Nature 326, 73–77 (1987). https://doi.org/10.1038/326073a0

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