Kobilka B K, Kobilka T S, Daniel K, Regan J W, Caron M G, Lefkowitz R J
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Science. 1988 Jun 3;240(4857):1310-6. doi: 10.1126/science.2836950.
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.
α2和β2肾上腺素能受体都可被肾上腺素激活，但可用选择性药物加以区分，它们对腺苷酸环化酶系统具有相反的作用（抑制性和刺激性）。这两种受体彼此同源，与视紫红质以及其他与鸟嘌呤核苷酸调节蛋白偶联的受体同源，它们含有七个疏水结构域，可能代表跨膜片段。在构建并表达一系列嵌合α2、β2肾上腺素能受体基因后，确定了这些受体特定结构域的功能。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个疏水结构域的氨基末端延伸至第六个疏水结构域的羧基末端的区域内。α2和β2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因素包含在第七个跨膜结构域内。嵌合受体应有助于阐明受体功能的结构基础。
