Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes
Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes
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DOI：
10.1016/j.cell.2005.12.037
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发表时间：
2006-03-10
期刊：
影响因子：
64.5
通讯作者：
Blacklow, SC
中科院分区：
文献类型：
--
作者：
Nam, Y;Sliz, P;Blacklow, SC
Notch受体通过形成一个复合体在相邻细胞之间传递必要的发育信号，该复合体在激活时导致靶基因的转录。我们报道了一种Notch转录激活复合体的晶体结构，该复合体包含人Notch1的Ankyrin结构域(ANK)、同源DNA上的转录因子CSL和辅助激活因子MasterMind-like-1(MAML-1)的多肽。CSL和ANK共同形成一个凹槽，以70A螺旋的形式结合MAML-1多肽。复合结合表面可能限制MAML蛋白招募到启动子上，其中Notch：CSL复合体已经预先组装，确保了对Notch靶基因的严格转录控制。
Notch receptors transduce essential developmental signals between neighboring cells by forming a complex that leads to transcription of target genes upon activation. We report here the crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1 (ANK), the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 (MAML-1). Together, CSL and ANK create a groove to bind the MAML-1 polypeptide as a kinked, 70 A helix. The composite binding surface likely restricts the recruitment of MAML proteins to promoters on which Notch:CSL complexes have been preassembled, ensuring tight transcriptional control of Notch target genes.