PRIMARY STRUCTURE AND BIOCHEMICAL-PROPERTIES OF AN M2 MUSCARINIC RECEPTOR
PRIMARY STRUCTURE AND BIOCHEMICAL-PROPERTIES OF AN M2 MUSCARINIC RECEPTOR
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DOI：
10.1126/science.3107123
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发表时间：
1987-05-01
期刊：
影响因子：
56.9
通讯作者：
CAPON, DJ
中科院分区：
文献类型：
--
作者：
PERALTA, EG;WINSLOW, JW;CAPON, DJ
利用获得的猪心房毒蕈碱乙酰胆碱受体的部分氨基酸序列，分离出含有完整受体编码区的互补DNA克隆。推断出的466个氨基酸多肽与鸟嘌呤核苷酸结合(G)蛋白偶联的其他受体具有广泛的结构和序列同源性。-肾上腺素能受体和视紫红质)；这种相似性预测了七个跨膜区域的结构，由一个大的细胞质域的配置来区分。心房受体互补DNA稳定转染中国仓鼠卵巢细胞系，导致毒蕈碱拮抗剂在这些细胞中结合，具有M2受体亚型的亲和力特征。心房毒蕈碱受体由一个独特的基因编码，该基因由单个编码外显子和多个可选拼接的5”非编码区组成。心房受体与脑毒蕈碱受体基因产物不同，只有38%的氨基酸同源性，并且处理一个完全非同源的大细胞质结构域，这表明后者在差异效应偶联中起作用。
A partial amino acid sequence obtained for porcine atrial muscarinic acetylcholine receptor was used to isolate complementary DNA clones containing the complete receptor coding region. The deduced 466-amino acid polypeptide exhibits extensive structural and sequence homology with other receptors coupled to guanine nucleotide binding (G) proteins (for example, the .beta.-adrenergic receptor and rhodopsins); this similarity predicts a structure of seven membrane-spanning regions distinguished by the disposition of a large cytoplasmic domain. Stable transfection of the Chinese hamster ovary cell line with the atrial receptor complementary DNA leads to the binding of muscarinic antagonists in these cells with affinities characteristic of the M2 receptor subtype. The atrial muscarinic receptor is encoded by a unique gene consisting of a single coding exon and multiple, alternatively spliced 5'' noncoding regions. The atrial receptor is distinct from the cerebral muscarinic receptor gene product, sharing only 38% overall amino acid homology and processing a completely nonhomologous large cytoplasmic domain, suggesting a role for the latter region in differential effector coupling.