Freedman L P, Luisi B F
Cell Biology and Genetics Program, Sloan-Kettering Institute, New York, New York 10021.
J Cell Biochem. 1993 Feb;51(2):140-50. doi: 10.1002/jcb.240510205.
The nuclear hormone receptor DNA-binding domain consists of two zinc finger-like modules whose amino acids are highly conserved among the members of the receptor superfamily. In this review, we describe the various genetic, biochemical, and structural experiments that have been carried out primarily for the DNA-binding domains of the glucocorticoid and estrogen receptors. We describe how the structural and functional information have permitted us to predict properties of the DNA-binding domains of other nuclear receptors. We postulate how receptors discriminate closely related response elements through sequence-specific contacts and distinguish symmetry of target sites through protein-protein interactions. This mechanism explains in part how the receptors regulate diverse sets of genes from a limited repertoire of core response elements. Lastly, we describe the stereochemical basis of nuclear receptor dysfunction in certain clinical disorders.
核激素受体DNA结合结构域由两个锌指样模块组成，其氨基酸在受体超家族成员中高度保守。在本综述中，我们描述了主要针对糖皮质激素和雌激素受体的DNA结合结构域所进行的各种遗传、生化和结构实验。我们阐述了结构和功能信息如何使我们能够预测其他核受体DNA结合结构域的特性。我们推测受体如何通过序列特异性接触区分密切相关的反应元件，并通过蛋白质-蛋白质相互作用区分靶位点的对称性。这一机制部分解释了受体如何从有限的核心反应元件库中调控多种基因集。最后，我们描述了某些临床疾病中核受体功能障碍的立体化学基础。
