HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations
HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations
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DOI：
10.1038/nsmb798
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发表时间：
2004-08-01
影响因子：
16.8
通讯作者：
Radhakrishnan, I
中科院分区：
文献类型：
--
作者：
Swanson, KA;Knoepfler, PS;Radhakrishnan, I
组蛋白去乙酰化酶（HDAC）相关的Sin 3辅阻遏物的募集是许多真核基因沉默途径中的必需步骤。在这里，我们表明，HBP 1，细胞周期抑制剂和分化调节剂，抑制转录HDAC/Sin 3依赖的方式，通过靶向哺乳动物Sin 3A（mSin 3A）PAH 2结构域。HBP 1与Mad 1阻遏物无关，Mad 1阻遏物与PAH 2复合的高分辨率结构已被描述。我们发现，像Mad 1，HBP 1反式阻遏结构域通过螺旋结构结合到mSin 3A PAH 2的疏水裂缝。值得注意的是，HBP 1螺旋以相对于Mad 1的反向方向结合PAH 2，同样出乎意料的是，这与最小Sin 3相互作用基序的链反转相关。这些结果不仅提供了深入了解如何多个，不相关的转录因子招聘相同的辅调节，但也有影响如何进行序列相似性搜索。
Recruitment of the histone deacetylase (HDAC)-associated Sin3 corepressor is an obligatory step in many eukaryotic gene silencing pathways. Here we show that HBP1, a cell cycle inhibitor and regulator of differentiation, represses transcription in a HDAC/Sin3-dependent manner by targeting the mammalian Sin3A (mSin3A) PAH2 domain. HBP1 is unrelated to the Mad1 repressor for which high-resolution structures in complex with PAH2 have been described. We show that like Mad1, the HBP1 transrepression domain binds through a helical structure to the hydrophobic cleft of mSin3A PAH2. Notably, the HBP1 helix binds PAH2 in a reversed orientation relative to Mad1 and, equally unexpectedly, this is correlated with a chain reversal of the minimal Sin3 interaction motifs. These results not only provide insights into how multiple, unrelated transcription factors recruit the same coregulator, but also have implications for how sequence similarity searches are conducted.