Structural basis for cooperative transcription factor binding to the CBP coactivator
Structural basis for cooperative transcription factor binding to the CBP coactivator
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DOI：
10.1016/j.jmb.2005.09.059
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发表时间：
2006-02-03
影响因子：
5.6
通讯作者：
Wright, PE
中科院分区：
文献类型：
--
作者：
De Guzman, RN;Goto, NK;Wright, PE
转录调控需要转录激活因子和转录辅激活因子CREB结合蛋白（CBP）之间的相互作用。CBP的KIX结构域可以同时结合两种不同的蛋白质，为转录调控提供了额外的机制。在这里，我们描述的三元复合物的解决方案结构的合作结合的激活结构域从c-Myb和混合谱系白血病（MLL）转录因子的KIX结构域形成的。MLL和c-Myb结构域形成结合到KIX相对面上的两个不同疏水凹槽的螺旋。与二元KIX：c-Myb复合物相比，在三元复合物的MLL结合界面处的KIX结构中观察到显著变化。在二元复合物中无序的KIX的两个区域在三元复合物中变得结构化：柔性环与结合的MLL形成紧密接触，并且C-末端螺旋通过MLL结合而延伸和稳定。这种结构变化的结果在KIX和结合的c-Myb之间形成额外的静电/极性相互作用，提供了一个结构基础的三元复合物观察到的协同性。(c)2005爱思唯尔有限公司保留所有权利。
Regulation of transcription requires interactions between transcriptional activators and transcriptional co-activator CREB binding protein (CBP). The KIX domain of CBP can bind simultaneously to two different proteins, providing an additional mechanism for transcriptional regulation. Here we describe the solution structure of the ternary complex formed by cooperative binding of activation domains from the c-Myb and mixed lineage leukemia (MLL) transcription factors to the KIX domain. The MLL and c-Myb domains form helices that bind to two distinct hydrophobic grooves on opposite faces of KIX. Compared to the binary KIX:c-Myb complex, significant changes are observed in the structure of KIX at the MLL binding interface in the ternary complex. Two regions of KIX that are disordered in the binary complex become structured in the ternary complex: a flexible loop forms intimate contacts with bound MLL, and the C-terminal helix is extended and stabilized by MLL binding. This structural change results in the formation of additional electrostatic/polar interactions between KIX and the bound c-Myb, providing a structural basis for the cooperativity observed for the ternary complex. (c) 2005 Elsevier Ltd. All rights reserved.