Naturally occurring osmolyte, trehalose induces functional conformation in an intrinsically disordered activation domain of glucocorticoid receptor.
Naturally occurring osmolyte, trehalose induces functional conformation in an intrinsically disordered activation domain of glucocorticoid receptor.
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DOI：
10.1371/journal.pone.0019689
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kumar R
中科院分区：
文献类型：
--
作者：
Khan SH;Arnott JA;Kumar R
内在无序（ID）区域经常出现在包括核激素受体在内的许多转录因子的激活域中。人们认为，这些ID区域通过创造适合与特定蛋白质结合伙伴相互作用的大表面来促进分子识别，这是转录因子基因调控的关键组成部分。据推测，这些活化结构域的条件折叠可能是它们与特定协同调节蛋白有效相互作用的先决条件，以及随后导致靶基因调节的转录活性。在这项研究中，我们测试了天然存在的渗透物海藻糖是否可以促进糖皮质激素受体主要激活功能域AF1的功能有序构象，AF1被发现作为ID蛋白存在，并且需要与协同调节蛋白有效相互作用才能获得最佳活性。我们的数据表明海藻糖诱导AF1的有序构象，使其与糖皮质激素受体活性的关键共调节剂类固醇受体共激活因子-1 （SRC-1）的相互作用大大增强。
Intrinsically disordered (ID) regions are frequently found in the activation domains of many transcription factors including nuclear hormone receptors. It is believed that these ID regions promote molecular recognition by creating large surfaces suitable for interactions with their specific protein binding partners, which is a critical component of gene regulation by transcription factors. It has been hypothesized that conditional folding of these activation domains may be a prerequisite for their efficient interaction with specific coregulatory proteins, and subsequent transcriptional activity leading to the regulation of target gene(s). In this study, we tested whether a naturally occurring osmolyte, trehalose can promote functionally ordered conformation in glucocorticoid receptor's major activation function domain, AF1, which is found to exist as an ID protein, and requires an efficient interaction with coregulatory proteins for optimal activity. Our data show that trehalose induces an ordered conformation in AF1 such that its interaction with steroid receptor coactivator-1 (SRC-1), a critical coregulator of glucocorticoid receptor's activity, is greatly enhanced.
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影响因子：
13.8
作者：
Baldwin, RL;Rose, GD
通讯作者：
Rose, GD
影响因子：
5.3
作者：
Garza, Anna M. S.;Khan, Shagufta H.;Kumar, Raj
通讯作者：
Kumar, Raj
影响因子：
64.5
作者：
Bledsoe, RK;Montana, VG;Xu, HE
通讯作者：
Xu, HE
DOI：
10.1152/ajprenal.1995.268.6.f983
发表时间：
1995-06-01
期刊：
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY
影响因子：
--
作者：
BURG, MB
通讯作者：
BURG, MB
影响因子：
4.8
作者：
Baskakov, IV;Kumar, R;Thompson, EB
通讯作者：
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