Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1.
Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1.
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通过转录因子SATB1识别DNA基质附着区域的结构基础。
DOI：
10.1093/nar/gkm504
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发表时间：
2007
影响因子：
14.9
通讯作者：
Harata, Kazuaki
中科院分区：
文献类型：
--
作者：
Yamasaki, Kazuhiko;Akiba, Toshihiko;Yamasaki, Tomoko;Harata, Kazuaki
特殊AT-rich sequence binding protein 1 （SATB1）通过结合DNA的基质附着区（matrix attachment regions, MARs）和诱导局部染色质重塑，调控免疫t细胞成熟和胎儿球蛋白种类转换所必需的基因表达。以前我们已经通过NMR揭示了人类SATB1的n端CUT结构域的五螺旋结构，该结构域本质上是mar结合结构域的折叠区域。在这里，我们确定了CUT结构域和MAR DNA复合物的晶体结构，其中CUT结构域的第三螺旋以b型深入DNA的主槽。5 ‘ -CTAATA-3 ’序列的碱基通过直接和水介导的氢键以及极性和范德华接触与该螺旋相连。保守的碱基接触残基Gln402和Gly403的突变降低了dna结合活性，这证实了观察到的涉及这些残基的相互作用的重要性。对于典型的四螺旋同源蛋白的特异性结构域，也观察到大量的等效接触，表明这些结构域具有DNA结合模式的共同框架，可以识别部分相似的DNA序列。
Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. Previously we have revealed a five-helix structure of the N-terminal CUT domain, which is essentially the folded region in the MAR-binding domain, of human SATB1 by NMR. Here we determined crystal structure of the complex of the CUT domain and a MAR DNA, in which the third helix of the CUT domain deeply enters the major groove of DNA in the B-form. Bases of 5′-CTAATA-3′ sequence are contacted by this helix, through direct and water-mediated hydrogen bonds and apolar and van der Waals contacts. Mutations at conserved base-contacting residues, Gln402 and Gly403, reduced the DNA-binding activity, which confirmed the importance of the observed interactions involving these residues. A significant number of equivalent contacts are observed also for typically four-helix POU-specific domains of POU-homologous proteins, indicating that these domains share a common framework of the DNA-binding mode, recognizing partially similar DNA sequences.