Dixon R A, Sigal I S, Rands E, Register R B, Candelore M R, Blake A D, Strader C D
Nature. 1987;326(6108):73-7. doi: 10.1038/326073a0.
Recently the genes for several hormone receptors that interact with guanine nucleotide binding proteins (G proteins) have been cloned, including the hamster beta 2-adrenergic receptor (beta 2AR), a human beta AR, the turkey erythrocyte beta AR and the porcine muscarinic acetylcholine receptor (MAR). All these receptors share some amino-acid homology with rhodopsin, particularly in 7 hydrophobic stretches of residues that are believed to represent transmembrane helices. 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 beta AR proteins, and a series of deletion mutant genes of the hamster beta 2AR. 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.
最近，几种与鸟嘌呤核苷酸结合蛋白（G蛋白）相互作用的激素受体基因已被克隆，包括仓鼠β2 - 肾上腺素能受体（β2AR）、人β肾上腺素能受体、火鸡红细胞β肾上腺素能受体和猪毒蕈碱型乙酰胆碱受体（MAR）。所有这些受体与视紫红质都有一些氨基酸同源性，特别是在7个疏水残基片段中，这些片段被认为代表跨膜螺旋。为了确定配体特异性的差异是否源于这些受体亲水区域序列的差异，我们在哺乳动物细胞中表达了野生型仓鼠和人β肾上腺素能受体蛋白的基因，以及仓鼠β2AR的一系列缺失突变基因。所表达受体的药理学表明，大多数亲水残基并不直接参与激动剂或拮抗剂与受体的结合。此外，我们还鉴定出一种具有高激动剂亲和力但不与腺苷酸环化酶偶联的突变受体。
