Osmolyte-induced folding of an intrinsically disordered activation function subdomain of glucocorticoid receptor.
Osmolyte-induced folding of an intrinsically disordered activation function subdomain of glucocorticoid receptor.
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渗透剂诱导的糖皮质激素受体的内在紊乱的激活功能子域的折叠。
DOI：
10.1080/10799890802412385
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Kumar,Raj
中科院分区：
文献类型：
--
作者：
Kumar,Raj
胞内无序（ID）区域在细胞信号蛋白中不成比例地高，这表明其调节能力中的重要作用。许多转录因子的激活结构域以ID构象存在。已经提出，ID激活结构域中的大的柔性区域比具有有序构象的蛋白质具有优势，使得ID区域/结构域可以与它们的靶配偶体进行更有效的相互作用。主要激活功能-1（AF 1）区位于包括糖皮质激素受体（GR）在内的多种类固醇受体的N端结构域，具有ID序列。最近，我们报道了渗透剂折叠AF 1成功能活性构象。大多数已知的AF 1：辅调节蛋白的相互作用发生在一个核心亚结构域（AF 1C），这是必不可少的AF 1介导的GR活动。然而，目前尚不清楚渗透剂是否可以诱导AF 1C的功能性折叠构象。在这项研究中，我们发现，一种天然存在的渗透剂，三甲胺-N-氧化物，可以合作折叠AF 1C成一个紧凑的结构。
Intrinsically disordered (ID) regions are disproportionately higher in cell-signaling proteins, suggesting an important role in their regulatory capacity. Activation domains of many transcription factors exist in ID conformation(s). It has been suggested that large flexible regions in ID activation domains have an advantage over proteins with ordered conformations such that ID regions/domains can make more efficient interactions with their target partners. The major activation function-1 (AF1) region, located in the N-terminal domain of several steroid receptors, including the glucocorticoid receptor (GR) possess ID sequences. Recently, we reported that osmolytes fold AF1 into functionally active conformation. Most of known AF1:coregulatory proteins interactions take place in a core subdomain (AF1C) that is indispensible for AF1-mediated GR activity. However, it is not known whether osmolytes can induce functionally folded conformation in AF1C. In this study we have found that a naturally occurring osmolyte, trimethylamine-N-oxide, can cooperatively fold AF1Cinto a compact structure.