Induced α-helix structure in AF1 of the androgen receptor upon binding transcription factor TFIIF
Induced α-helix structure in AF1 of the androgen receptor upon binding transcription factor TFIIF
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DOI：
10.1021/bi035934p
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发表时间：
2004-03-23
期刊：
影响因子：
2.9
通讯作者：
McEwan, IJ
中科院分区：
文献类型：
--
作者：
Kumar, R;Betney, R;McEwan, IJ
近年来，人们已经清楚地认识到，在许多蛋白质中，重要区域是由氨基酸序列编码的，这些氨基酸序列不会自动折叠成完全浓缩的功能结构。表征非小叶蛋白序列的构象倾向和功能是一个主要的挑战。在具有未折叠区域的蛋白质中突出的是许多转录因子，包括类固醇受体。在许多情况下，这些蛋白质的未折叠或部分折叠区域在蛋白质与其适当的结合伙伴（即它必须与之结合以执行其功能的分子）相互作用时形成。雄激素受体（AR）的AF1结构域以重组肽的形式表达时，显示出很少的结构。先前已经证明AF1在体外与转录因子TFIIF相互作用。利用傅里叶变换红外（FTIR），我们测试了这种相互作用是否可以诱导araf1的结构。我们的研究结果表明，重组AR AF1在与TFIIF复合物的亚基RAP74相互作用后可以获得显著更高的螺旋含量。我们进一步表明，在araf1中诱导的这种构象非常适合与SRC-1相互作用。
In recent years, it has become clear that in many proteins, significant regions are encoded by amino acid sequences that do not automatically fold into their fully condensed, functional structures. Characterization of the conformational propensities and function of the nonglobular protein sequences represents a major challenge. Striking among proteins with unfolded regions are numbers of transcription factors, including steroid receptors. In many cases, the unfolded or partially folded regions of such proteins take shape when the protein interacts with its proper binding partner(s), that is, the molecules to which it must bind to carry out its function. The AF1 domain of the androgen receptor (AR) shows little structure, when expressed as a recombinant peptide. It has been shown previously that AF1 interacts with transcription factor TFIIF in vitro. Using Fourier transform infrared (FTIR), we tested whether this interaction can induce structure in the AR AF1. Our results demonstrate that the recombinant AR AF1 can acquire significantly higher helical content after interacting with RAP74, a subunit of the TFIIF complex. We further show that this induced conformation in the AR AF1 is well-suited for its interaction with SRC-1.