Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4
Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4
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转录因子 Sp1 和 TAF4 内在无序区域之间的相互作用
DOI：
10.1002/pro.3013
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发表时间：
2016
期刊：
影响因子：
8
通讯作者：
and M. Hoshino
中科院分区：
文献类型：
--
作者：
E. Hibino;R. Inoue;M. Sugiyama;J. Kuwahara;K. Matsuzaki;and M. Hoshino
真核基因的表达是由一般转录起始因子和基因特异性转录激活因子之间的特异性相互作用精确控制的。一般转录因子TFIID在介导转录激活中起重要作用，是一种多亚基复合物，包含TATA盒结合蛋白（TBP）和多种TBP相关因子（TAF）。另一方面，生物化学和遗传学方法已经表明，启动子特异性转录激活因子Sp1能够与TFIID的一种成分TBP相关因子TAF 4相互作用。本文中，我们使用圆二色性（CD）和异相磁共振（NMR）光谱报告了Sp1和TAF 4的富含谷氨酰胺结构域（Q-结构域）的结构细节。我们发现，在生理条件下，Sp1的两个Q-结构域和TAF 4的四个Q-结构域是无序的。我们还通过NMR和表面等离子体共振定量分析了Sp1和TAF 4的Q-结构域之间的相互作用，并检测到它们之间微弱但特异的缔合。然而，CD光谱的详细分析表明，任何显着的构象变化并没有伴随着这种关联发生，至少在整体二级结构的水平。这些结果可能代表了IDP的突出和特殊的结合模式，其未被归类为公认的“偶联折叠和结合”概念。
The expression of eukaryotic genes is precisely controlled by specific interactions between general transcription initiation factors and gene‐specific transcriptional activators. The general transcription factor TFIID, which plays an essential role in mediating transcriptional activation, is a multisubunit complex comprising the TATA box‐binding protein (TBP) and multiple TBP‐associated factors (TAFs). On the other hand, biochemical and genetic approaches have shown that the promoter‐specific transcriptional activator Sp1 has the ability to interact with one of the components of TFIID, the TBP‐associated factor TAF4. We herein report the structural details of the glutamine‐rich domains (Q‐domains) of Sp1 and TAF4 using circular dichroism (CD) and heteronuclear magnetic resonance (NMR) spectroscopy. We found that the two Q‐domains of Sp1 and four Q‐domains of TAF4 were disordered under physiological conditions. We also quantitatively analyzed the interaction between the Q‐domains of Sp1 and TAF4 by NMR and surface plasmon resonance, and detected a weak but specific association between them. Nevertheless, a detailed analysis of CD spectra suggested that any significant conformational change did not occur concomitantly with this association, at least at the level of the overall secondary structure. These results may represent a prominent and exceptional binding mode for the IDPs, which are not categorized in a well‐accepted concept of “coupled folding and binding.”