Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA-18510, USA.
Mol Cell Endocrinol. 2012 Jan 30;348(2):450-6. doi: 10.1016/j.mce.2011.03.024. Epub 2011 Apr 8.
The glucocorticoid receptor (GR) mediates biological effects of glucocorticoids at the level of gene regulation, and plays important roles in many aspects of physiology. In recent years, it has become quite evident that GR behaves very dynamically, controlled by its reversible interactions with a variety of coregulatory proteins at various DNA and non-DNA sites. The N-terminal activation function domain (AF1) of the GR exists in an intrinsically disordered (ID) state, which promotes molecular recognition by providing surfaces capable of binding specific target molecules. Several studies suggest that when in action, the GR AF1 gains structure. Thus, it is hypothesized that the GR AF1 domain may be structured in vivo, at least when directly involved in transcriptional activation. Our recent work supports this conclusion. We propose that by allowing AF1 to rapidly and reversibly adopt various configurations through structural arrangements, AF1 can create protein surfaces that are readily available for selective binding to coregulatory proteins, resulting in GR-mediated transcriptional regulation of target genes.
糖皮质激素受体（GR）在基因调控水平上介导糖皮质激素的生物学效应，在许多生理方面发挥着重要作用。近年来，GR 非常活跃，其通过与各种核心调节蛋白在各种 DNA 和非 DNA 位点的可逆相互作用得到很好的控制，这一点已经变得非常明显。GR 的 N 端激活功能域（AF1）处于固有无序（ID）状态，通过提供能够与特定靶分子结合的表面，促进分子识别。几项研究表明，当处于活动状态时，GR AF1 会获得结构。因此，有人假设 GR AF1 结构域在体内可能是有结构的，至少当它直接参与转录激活时是如此。我们最近的工作支持这一结论。我们提出，通过允许 AF1 通过结构排列快速且可逆地采用各种构象，AF1 可以创建可供核心调节蛋白选择性结合的蛋白质表面，从而导致 GR 介导的靶基因转录调控。
