CHIMERIC ALPHA-2-ADRENERGIC, BETA-2-ADRENERGIC RECEPTORS - DELINEATION OF DOMAINS INVOLVED IN EFFECTOR COUPLING AND LIGAND-BINDING SPECIFICITY
CHIMERIC ALPHA-2-ADRENERGIC, BETA-2-ADRENERGIC RECEPTORS - DELINEATION OF DOMAINS INVOLVED IN EFFECTOR COUPLING AND LIGAND-BINDING SPECIFICITY
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DOI：
10.1126/science.2836950
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发表时间：
1988-06-03
期刊：
影响因子：
56.9
通讯作者：
LEFKOWITZ, RJ
中科院分区：
文献类型：
--
作者：
KOBILKA, BK;KOBILKA, TS;LEFKOWITZ, RJ
α 2和β 2肾上腺素能受体均被肾上腺素激活，但可被选择性药物区分，它们对腺苷酸环化酶系统具有相反的作用（抑制和刺激）。这两种受体彼此同源，视紫红质和与鸟嘌呤核苷酸调节蛋白偶联的其他受体，并且它们含有七个疏水结构域，其可以代表跨膜区段。在构建和表达一系列嵌合α 2-，β 2-肾上腺素能受体基因后，确定这些受体的特定结构域的功能。与刺激性鸟嘌呤核苷酸调节蛋白偶联的特异性位于从第五疏水结构域的氨基末端延伸至第六疏水结构域的羧基末端的区域内。α 2-和β 2-肾上腺素能受体激动剂和拮抗剂配体结合特异性的主要决定子包含在第七跨膜结构域内。 嵌合受体应证明是有用的，阐明受体功能的结构基础。
The .alpha.2 and .beta.2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric .alpha.2-,.beta.2-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of .alpha.2- and .beta.2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.