Structural insights into glucocorticoid receptor function.
Structural insights into glucocorticoid receptor function.
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DOI：
10.1042/bst20210419
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发表时间：
2021-11-01
影响因子：
3.9
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中科院分区：
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糖皮质激素受体（GR）是类固醇激素激活的转录因子，其结合各种糖皮质激素反应元件以上调或下调参与代谢、发育、应激和炎症反应的数千个基因的转录。GR由两个结构域组成，能够与糖皮质激素、DNA反应元件和辅助调节因子相互作用，以及介导冷凝物形成的大的固有无序区域。在过去的十年中，越来越多的结构研究为GR相互作用提供了新的线索，为驱动特定环境GR活性的机制提供了新的理解。在这里，我们主要从结构的角度总结了GR的既定和新出现的作用机制。这篇小综述还讨论了目前对GR功能的认识如何指导未来的糖皮质激素设计，以改善不同炎症性疾病的治疗指数。
The glucocorticoid receptor (GR) is a steroid hormone-activated transcription factor that binds to various glucocorticoid response elements to up- or down- regulate the transcription of thousands of genes involved in metabolism, development, stress and inflammatory responses. GR consists of two domains enabling interaction with glucocorticoids, DNA response elements and coregulators, as well as a large intrinsically disordered region that mediates condensate formation. A growing body of structural studies during the past decade have shed new light on GR interactions, providing a new understanding of the mechanisms driving context-specific GR activity. Here, we summarize the established and emerging mechanisms of action of GR, primarily from a structural perspective. This minireview also discusses how the current state of knowledge of GR function may guide future glucocorticoid design with an improved therapeutic index for different inflammatory disorders.