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首页> 外文期刊>The Biochemical Journal >The crystal structure of the Sox4 HMG domain-DNA complex suggests aTI The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition
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The crystal structure of the Sox4 HMG domain-DNA complex suggests aTI The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition

机译：Sox4 HMG域-DNA复合物的晶体结构表明aTI Sox4 HMG域-DNA复合物的晶体结构表明DNA识别中位置相互依赖的机制

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摘要

It has recently been proposed that the sequence preferences of DNA-binding TFs (transcription factors) can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. In the present study we examine the crystal structure of the HMG (high-mobility group) domain of Sox4 [Sry (sex-determining region on the Y chromosome)-related HMG box 4] bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2, we observed subtle conformational differences at the DNA-binding interface. Furthermore, using quantitative electrophoretic mobility-shift assays we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These results suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adaptations lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs.
机译：最近已经提出，可以通过包括靶位点的核苷酸的位置相互依赖性的模型很好地描述DNA结合TF（转录因子）的序列偏好。这样的结合模型允许调用多个基序，例如在两个或更多个核苷酸位置处不同的主要和次级基序。但是，TF修饰此类变异基序的结构机制仍然难以捉摸。在本研究中，我们研究了与DNA结合的Sox4 [Sry（Y染色体上的性别决定区域）相关HMG盒4]的HMG（高迁移率族）域的晶体结构。通过比较此结构与以前解决的Sox17和Sox2结构，我们观察到了DNA结合界面上的细微构象差异。此外，使用定量电泳迁移率变动分析，我们验证了两个核苷酸的位置相互依赖性以及Sox4亲和力环境中次要Sox基序的存在。这些结果表明，两个界面氨基酸的一致重排使Sox4能够容纳一级和二级基序。结构的适应性导致改变的二核苷酸偏好彼此相辅相成。这些分析强调了TF识别DNA的复杂性，并为位置相互依赖和二级结合基序的概念框架提供了实验验证。

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