Structurally distinct modes of recognition of the KIX domain of CBP by Jun and CREB
Structurally distinct modes of recognition of the KIX domain of CBP by Jun and CREB
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DOI：
10.1021/bi026222m
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发表时间：
2002-11-26
期刊：
影响因子：
2.9
通讯作者：
Lumb, KJ
中科院分区：
文献类型：
--
作者：
Campbell, KM;Lumb, KJ
基因表达部分地通过转录激活因子和其他转录因子如辅激活因子之间的相互作用来协调。共激活因子和组蛋白乙酰转移酶CREB结合蛋白（CBP）的KIX结构域结合许多哺乳动物和病毒转录激活因子，如BRCA 1、CREB、c-Jun、c-Myb、p53、乳头瘤病毒E2和HTLV-1 Tax。CREB-CBP复合物的形成取决于CREB的KID区域的磷酸化，并且涉及在结合CBP的KIX结构域的疏水沟后诱导KID折叠。在这里，我们研究了由人KIX和人c-Jun的N-末端激活结构域形成的复合物的形成。圆二色性光谱表明，Jun N-末端激活结构域本质上是无序的隔离和KIX结合是独立的Jun磷酸化。与CREB表现出的结合模式相反，NMR化学位移图表明，c-Jun活化结构域与CREB所用的KIX表面结合明显不同。此外，NMR和沉降平衡研究表明，c-Jun和CREB的激活结构域可以同时结合CBP的KIX结构域。结果说明了一种新的模式的结合和组合招聘通过KIX结构域的CBP的多个转录激活因子。
Gene expression is coordinated in part by interactions between transcriptional activators and other transcription factors such as coactivators. The KIX domain of the coactivator and histone acetyltransferase CREB binding protein (CBP) binds numerous mammalian and viral transcriptional activators such as BRCA1, CREB, c-Jun, c-Myb, p53, papillomavirus E2, and HTLV-1 Tax. Formation of the CREB-CBP complex depends on phosphorylation of the KID region of CREB and involves induced folding of KID upon binding a hydrophobic groove of the KIX domain of CBP. Here we investigate the formation of the complex formed by human KIX and the N-terminal activation domain of human c-Jun. The c-Jun activation domain and KID do not share significant sequence similarity. Circular dichroism spectroscopy shows that the Jun N-terminal activation domain is intrinsically disordered in isolation and that KIX binding is independent of Jun phosphorylation. In contrast to the mode of binding exhibited by CREB, NMR chemical shift mapping indicates that the c-Jun activation domain binds to a distinctly different surface of KIX than used by CREB. Moreover, NMR and sedimentation equilibrium studies show that the activation domains of c-Jun and CREB can simultaneously bind the KIX domain of CBP. The results illustrate a new mode of binding and combinatorial recruitment via the KIX domain of CBP by multiple transcriptional activators.