Intra-domain communication between the N-terminal and DNA-binding domains of the androgen receptor: modulation of androgen response element DNA binding
Intra-domain communication between the N-terminal and DNA-binding domains of the androgen receptor: modulation of androgen response element DNA binding
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DOI：
10.1677/jme.1.01723
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发表时间：
2005-06-01
影响因子：
3.5
通讯作者：
McEwan, IJ
中科院分区：
文献类型：
--
作者：
Brodie, J;McEwan, IJ
雄激素受体（AR）是一种配体激活的转录因子，在类固醇睾酮或双氢睾酮的激活下识别并结合特定的DNA应答元件。在体外，已经发现了两种类型的反应元件——结合雄激素、糖皮质激素和孕激素受体的非选择性元件，以及雄激素受体选择性序列。本文研究了DNA结合对受体氨基末端结构域（NTD）的变构效应。与这两种类型的DNA响应元件结合导致AR-NTD内四个色氨酸残基的固有荧光发射光谱发生变化，并导致更具蛋白酶抗性的构象。在结合实验中，我们观察到AR-NTD的存在降低了受体多肽分别与来自probasin、PEM和前列腺素C3基因的选择性和非选择性DNA元件结合的亲和力，而没有显著改变蛋白质碱基对的接触。综上所述，这些结果突出了AR-NTD和DNA结合域之间的域内通信在受体结构和功能中的作用。
The androgen receptor (AR) is a ligand-activated transcription factor that recognises and binds to specific DNA response elements upon activation by the steroids testosterone or dihydrotestosterone. In vitro, two types of response element have been characterised - non-selective elements that bind the androgen, glucocorticoid and progesterone receptors, and androgen receptor-selective sequences. In the present study, the allosteric effects of DNA binding on the receptor amino-terminal domain (NTD) were studied. Binding to both types of DNA response element resulted in changes in the intrinsic fluorescence emission spectrum for four tryptophan residues within the AR-NTD and resulted in a more protease-resistant conformation. In binding experiments, it was observed that the presence of the AR-NTD reduced the affinity of receptor polypeptides for binding to both selective and non-selective DNA elements derived from the probasin, PEM and prostatin C3 genes respectively, without significantly altering the protein-base pair contacts. Taken together, these results highlight the role of intra-domain communications between the AR-NTD and the DNA binding domain in receptor structure and function.