Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: A model for activator:Coactivator interactions
Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: A model for activator:Coactivator interactions
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DOI：
10.1016/s0092-8674(00)80463-8
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发表时间：
1997-12-12
期刊：
影响因子：
64.5
通讯作者：
Wright, PE
中科院分区：
文献类型：
--
作者：
Radhakrishnan, I;PerezAlvarado, GC;Wright, PE
核因子CREB激活靶基因的转录，部分是通过与共激活因子CBP的KIX结构域以磷酸化依赖的方式直接相互作用。由CREB的磷酸化激酶诱导结构域（pKID）与KIX形成的复合物的溶液结构揭示，pKID在与KIX结合时经历卷曲->螺旋折叠转变，形成两个α螺旋。pKID的两亲性螺旋α B与由KIX的螺旋α 1和α 3限定的疏水沟相互作用。另一个pKID螺旋，α A，接触α 3螺旋的不同面。pKID的关键磷酸丝氨酸残基的磷酸基团与KIX的Tyr-658侧链形成氢键。该结构为其他反式激活结构域与其靶标之间的相互作用提供了模型。
The nuclear factor CREB activates transcription of target genes in part through direct interactions with the KIX domain of the coactivator CBP in a phosphorylation-dependent manner. The solution structure of the complex formed by the phosphorylated kinase-inducible domain (pKID) of CREB with KIX reveals that pKID undergoes a coil-->helix folding transition upon binding to KIX, forming two alpha helices. The amphipathic helix alpha B of pKID interacts with a hydrophobic groove defined by helices alpha 1 and alpha 3 of KIX. The other pKID helix, alpha A, contacts a different face of the alpha 3 helix. The phosphate group of the critical phosphoserine residue of pKID forms a hydrogen bond to the side chain of Tyr-658 of KIX. The structure provides a model for interactions between other transactivation domains and their targets.