Architectural Principles for the Structure and Function of the Glucocorticoid Receptor τ1 Core Activation Domain*
Architectural Principles for the Structure and Function of the Glucocorticoid Receptor τ1 Core Activation Domain*
复制标题
糖皮质激素受体 τ1 核心激活域的结构和功能的架构原理*
DOI：
10.1074/jbc.m001007200
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
A. Wright
中科院分区：
文献类型：
--
作者：
A. Wärnmark;Jan;A. Wright
58个氨基酸的区域介导糖皮质激素受体τ1激活结构域的核心反式激活活性。该τ1核心结构域在水性缓冲液中是非结构化的，但在三氟乙醇的存在下诱导出三个α-螺旋片段。这些推定的结构模块中的两个已被测试在不同的组合方面的transactivation potentialin体内和体外的coactivators的结合能力。结果表明，虽然单个模块没有转录活性，但两个或三个模块的任何组合都是足够的，其中三模块构建体具有最高活性。然而，含有一个、两个或三个片段的蛋白质以相似的亲和力结合Ada 2和cAMP反应元件结合蛋白。因此，单个片段能够结合靶因子，但不能显著地反式激活靶基因。结果是一致的模型，其中激活域是由短激活模块，允许多种相互作用与coactivators。我们的研究结果还表明，模块的数量增加可能不会导致相应的更高的亲和力，而是结合位点的浓度增加，这会导致更高的结合率。这与其中激活剂-靶因子相互作用的结合速率而不是平衡常数是激活剂效力的最相关量度的模型一致。
A 58-amino acid region mediates the core transactivation activity of the glucocorticoid receptor τ1 activation domain. This τ1 core domain is unstructured in aqueous buffers, but in the presence of trifluoroethanol three α-helical segments are induced. Two of these putative structural modules have been tested in different combinations with regard to transactivation potentialin vivo and binding capacity to the coactivators in vitro. The results show that whereas single modules are not transcriptionally active, any combination of two or three modules is sufficient, with trimodular constructs having the highest activity. However, proteins containing one, two, or three segments bind Ada2 and cAMP-response element-binding protein with similar affinity. A single segment is thus able to bind a target factor but cannot transactivate target genes significantly. The results are consistent with models in which activation domains are comprised of short activation modules that allow multiple interactions with coactivators. Our results also suggest that an increased number of modules may not result in correspondingly higher affinity but instead that the concentration of binding sites is increased, which gives rise to a higher association rate. This is consistent with a model where the association rate for activator-target factor interactions rather than the equilibrium constant is the most relevant measure of activator potency.
DOI：
10.1073/pnas.90.3.883
发表时间：
1993-02-01
影响因子：
11.1
作者：
REGIER, JL;SHEN, F;TRIEZENBERG, SJ
通讯作者：
TRIEZENBERG, SJ
影响因子：
56.9
作者：
CRESS, WD;TRIEZENBERG, SJ
通讯作者：
TRIEZENBERG, SJ
影响因子：
10.5
作者：
NERLOV, C;ZIFF, EB
通讯作者：
ZIFF, EB