Bain David L, Heneghan Aaron F, Connaghan-Jones Keith D, Miura Michael T
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Annu Rev Physiol. 2007;69:201-20. doi: 10.1146/annurev.physiol.69.031905.160308.
Small lipophilic molecules such as steroidal hormones, retinoids, and free fatty acids control many of the reproductive, developmental, and metabolic processes in eukaryotes. The mediators of these effects are nuclear receptor proteins, ligand-activated transcription factors capable of regulating the expression of complex gene networks. This review addresses the structure and structural properties of nuclear receptors, focusing on the well-studied ligand-binding and DNA-binding domains as well as our still-emerging understanding of the largely unstructured N-terminal regions. To emphasize the allosteric interdependence among these subunits, a more detailed inspection of the structural properties of the human progesterone receptor is presented. Finally, this work is placed in the context of developing a quantitative and mechanistic understanding of nuclear receptor function.
诸如甾体激素、类视黄醇和游离脂肪酸等亲脂性小分子控制着真核生物中的许多生殖、发育和代谢过程。这些效应的介导物是核受体蛋白,即能够调节复杂基因网络表达的配体激活转录因子。本综述阐述了核受体的结构和结构特性,重点关注研究充分的配体结合域和DNA结合域,以及我们对基本上无结构的N端区域的逐渐深入的理解。为强调这些亚基之间的变构相互依赖性,本文对人孕酮受体的结构特性进行了更详细的考察。最后,将这项工作置于对核受体功能进行定量和机制理解的背景中。